Prognostic effect of masked morning hypertension in Chinese inpatients with non-dialysis chronic kidney disease: A multi-center retrospective study.

OBJECTIVE: This study aimed to elucidate the prognostic role of Masked Morning Hypertension (MMH) in non-dialysis-dependent chronic kidney disease (NDD-CKD). METHODS: 2,130 NDD-CKD patients of inpatient department were categorized into four blood pressure groups: clinical normotension (CH-), clinical hypertension (CH+) with morning hypertension (MH+), and without MH+ (MH-) respectively. The correlation between these four blood pressure types and the primary (all-cause mortality) and secondary endpoints (cardio-cerebrovascular disease [CVD] and end-stage kidney disease [ESKD]) was analyzed. RESULTS: The prevalences of morning hypertension and masked morning hypertension were 47.4% and 14.98%, respectively. Morning hypertension independently increased the risk of all-cause mortality (P=0.004) and CVD (P<0.001) but not ESKD (P=0.092). Masked morning hypertension was associated with heightened all-cause mortality (HR = 4.22, 95% CI = 1.31-13.59; P=0.02) and CVD events (HR = 5.14, 95% CI = 1.37-19.23; P=0.02), with no significant association with ESKD (HR = 1.18, 95% CI = 0.65-2.15; P=0.60). When considering non-CVD deaths as a competing risk factor, a high cumulative incidence of CVD events was observed in the masked morning hypertension group (HR = 5.16, 95% CI = 1.39-19.08). CONCLUSIONS: MMH is an independent risk factor for all-cause mortality and combined cardiovascular and cerebrovascular events in NDD-CKD patients, underscoring its prognostic significance. This highlights the need for comprehensive management of morning hypertension in this population.

Control status of ambulatory blood pressure and its relationship with arterial stiffness in the China nationwide registry of treated hypertensive patients: the REACTION-ABP study.

The control rate of ambulatory blood pressure (BP) is unclear in Chinese hypertensive patients, and whether it would be associated with the ambulatory arterial stiffness indices is also unknown. From June 2018 until December 2022, 4408 treated hypertensive patients (52.8% men, average age 58.2 years) from 77 hospitals in China were registered. Ambulatory BPs were measured with validated monitors and analyzed with a web-based standardized Shuoyun system ( www.shuoyun.com.cn ). The BP control rate was the highest in the office (65.7%), moderate in the daytime (45.0%), low in the morning (34.1%), and the lowest in the nighttime (27.6%, P < 0.001). Only 21.0% had their 24 h BP perfectly controlled. The stepwise regression analyses identified that the factors associated with an imperfect 24 h BP control included male sex, smoking and drinking habits, a higher body mass index, serum total cholesterol and triglycerides, and the use of several specific types of antihypertensive drugs. After adjustment for the above-mentioned factors, the 24 h pulse pressure (PP) and its components, the elastic and stiffening PPs, were all significantly associated with an uncontrolled office and ambulatory BP status with the standardized odds ratios ranging from 1.09 to 4.68 (P < 0.05). The ambulatory arterial stiffness index (AASI) was only associated with an uncontrolled nighttime and 24 h BP status. In conclusion, the control rates of 24 h ambulatory BP, especially that in the nighttime and morning time windows, were low in Chinese hypertensive patients, which might be associated with arterial stiffness in addition to other common risk factors.

Association of morning hypertension with chronic kidney disease progression and cardiovascular events in patients with chronic kidney disease and hypertension.

BACKGROUND AND AIM: Associations of morning hypertension with chronic kidney disease are rarely investigated in prospective studies. We aim to investigate the predictive value of uncontrolled morning hypertension (UMH) to chronic kidney disease (CKD) progression and cardiovascular (CV) events in patients with CKD and hypertension. METHODS AND RESULTS: In this prospective two-center observational study, 304 hypertensive patients with CKD were enrolled. Time to total mortality, CKD progression and CV events was recorded; Kaplan-Meier survival function estimates and Multivariable Cox proportional hazard model were used to investigate associations between UMH and outcomes. The study protocol was approved by the Institutional Review Board (http://www.thaiclinicaltrials.org; TCTR20180313004). After a follow-up for median 30 months, 23 (7.6%) patients died, 34 (11.2%) had CKD progression, and 95 (31.3%) occurred new-onset CV events, respectively. UMH was shown to be a strong predictor of CKD progression [hazard ratio (HR) 2.46, 95% confidence interval (CI) 1.22-4.94] and CV events (HR 1.69, 95% CI 1.12-2.53). When morning hypertension was analyzed as a continuous variable, morning systolic blood pressure (per 10 mmHg) was also shown to be predictive to CKD progression (HR 1.28, 95% CI 1.07-1.53, P < 0.01) and CV events (HR 1.15, 95% CI 1.03-1.28, P < 0.01). CONCLUSIONS: UMH is strongly associated with CKD progression and CV events in patients with CKD and hypertension. UMH in CKD patients deserves further attentions.

Pulsatile Chronotherapeutic Drug Delivery for Controlling Early Morning Surge in Blood Pressure; Effect of Coating on Eplerenone In-vitro, In-vivo Release and Urinary Na/K Ratio

Abstract The objective of the present study was to develop time delayed chronotherapeutic formulation of Eplerenone (Ep) to provide rapid drug release after a pre-determined lag time for the treatment of early morning hypertension. Cyclodextrin complexation was used to prepare fast release Ep core tablets. The developed core tablets were then coated with different rate-controlling polymers using compression coating technique. The developed tablets were evaluated for hardness, friability, drug content and swelling index. The in-vitro drug release was carried out to study the effect of different coating materials on drug release and lag time. Tablets selected for stability study were those showing lag time of 5-7 hours followed by complete drug release; F2, F3, F7, F8, and F12. The in-vivo study was carried out on tablets with the highest t90 as compared to commercial tablets after being administered to healthy human volunteers where plasma Ep and urinary Na/K ratio were determined. Results suggested that this approach was able to provide delayed release Ep formulations that will be useful for patients with morning surge in blood pressure.

The Association of Morning Hypertension With Target Organ Damage in Patients With Chronic Kidney Disease and Hypertension.

Objectives: To determine the association between morning hypertension and target organ damage (TOD) in patients with chronic kidney disease (CKD) and hypertension. Methods: In this cross-sectional study, 447 patients with CKD and hypertension from two centers were enrolled. Ambulatory blood pressure monitoring was conducted in all patients. Linear regression and logistic regression analysis were used to determine the association between morning hypertension and TOD in patients with CKD and hypertension, including assessments of estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), urine protein/creatinine ratio (UPCR), and left ventricular hypertrophy (LVH). Results: Overall, 194 (43.4%) participants had morning hypertension. Morning hypertension was strongly correlated with LVH [odds ratio (OR), 2.14; 95% confidence interval (CI), 1.3-3.51; p < 0.01], lower level of eGFR (ß = -0.51; 95%CI, -0.95--0.08; p < 0.05), higher LVMI (ß = 0.06; 95%CI, 0.04-0.08, p < 0.001), and UPCR (ß = 0.22; 95%CI, 0.06-0.38, p < 0.01), independent of nocturnal hypertension and elevated morning blood pressure surge. As a continuous variable, both morning systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found to be associated with LVH and higher level of UPCR and LVMI (p < 0.05), whereas only morning SBP was negatively correlated with eGFR (p < 0.01). Conclusion: Morning hypertension was strongly correlated with cardiac damage and impaired kidney function in CKD patients with hypertension, independent of nocturnal hypertension and morning surge in blood pressure. Morning hypertension in CKD patients warrants further attention.

Different effects of morning and nocturnal hypertension on target organ damage in chronic kidney disease.

Both morning hypertension (MH) and nocturnal hypertension (NH) are associated with severe target organ damage in patients with chronic kidney disease (CKD). However, the isolated or combined effects of MH and NH on target organ damage are less well-defined. A cross-sectional study was conducted among 2386 non-dialysis CKD patients with ambulatory blood pressure monitoring. The authors categorized patients into four groups based on the presence or absence of MH and NH. Multivariate logistic analyses were used to evaluate the correlation between hypertension subtypes and target organ damage, including left ventricular hypertrophy (LVH), abnormal carotid intima-media thickness (CIMT), low estimated glomerular filtration rate (eGFR), and albuminuria. The percentages of isolated MH, isolated NH, and combined MH and NH were 2.3%, 24.0%, and 49.3%, respectively. Compared to patients without MH and NH, isolated MH was only related to low eGFR (2.26 [95% confidence interval: 1.00-5.09]) and albuminuria (2.17 [95% CI: 1.03-4.54]). Meanwhile, combined MH and NH group compared to the group without MH and NH had a higher risk of LVH (2.87 [95% CI: 2.01-4.09]), abnormal CIMT (2.01 [95% CI: 1.47-2.75]), low eGFR (3.18 [95% CI: 2.23-4.54]), and albuminuria (1.79 [95% CI: 1.33-2.40]), even in patients without daytime hypertension. The risk of cardiovascular and renal damage was also observed in the isolated NH group. In conclusion, morning hypertension is associated with kidney dysfunction and has combined effects with nocturnal hypertension on cardiovascular damage in chronic kidney disease patients.

Systemic hemodynamic atherothrombotic syndrome (SHATS) - Coupling vascular disease and blood pressure variability: Proposed concept from pulse of Asia.

Hypertension (HTN) is an important risk factor for cardiovascular disease (CVD) but the association between HTN and CVD cannot be explained by average blood pressure (BP) alone. BP variability (BPV) is another important factor, along with the effects of HTN on the vasculature. The concept of systemic hemodynamic atherothrombotic syndrome (SHATS) has been proposed, describing an age-related and synergistic vicious cycle of hemodynamic stress and vascular disease. The importance of SHATS is based on the assumption that the assessment of BPV and arterial disease is likely to provide an effective opportunity to intervene early to reduce progression to HTN in younger patients or to CVD events and organ damage in older patients. In addition to providing an overview of current evidence for the mechanisms and clinical data related to SHATS, this article proposes a new SHATS score for use to diagnose and assess the severity of SHATS. The score includes two components - a BP score and a vascular score - which are multiplied to generate the SHATS score. This reflects the synergistic, rather than additive, effects of BP and vascular disease on target organ damage and CVD events. Although it requires refinement and validation in future studies, early detection of SHATS using tools such as the proposed score, combined with population-based stratification and technology-based anticipation medicine incorporating real-time individual data, has the potential to contribute to meaningful reductions in rates of CVD events and target organ damage.

Management of morning hypertension: a consensus statement of an Asian expert panel.

Morning blood pressure (BP) surge is an important aspect of hypertension research. Morning BP monitoring could be a clinically relevant concept in the therapeutic management of hypertension and in the prevention of cardiovascular complications by defining and treating morning hypertension. Because antihypertensive medication is often taken in the morning, uncontrolled morning BP during the trough effect hours could be a hallmark of inadequate choice of antihypertensive regimen, such as the use of short- or intermediate-acting drugs, underdosing of drugs, or no use or underuse of combination therapy. To improve the management of hypertension in general and morning hypertension in particular, long-acting antihypertensive drugs should be used in appropriate, often full dosages and in proper combinations. The clinical usefulness of antihypertensive drugs with specific mechanisms for morning BP or split or timed dosing of long-acting drugs in controlling morning BP remains under investigation.

The preliminary study of management model of morning hypertension in people with essential hypertension / 中国基层医药

Objective To analyze the epidemiological characteristics of morning hypertension in people with eseential hypertension in Dali Bai autonomous prefecture,and to study the management model for morning hypertension. Methods From May 2015 to January 2017,302 patients with hypertension in the People's Hospital of Dali Bai Autonomous Prefecture were divided voluntarily into two groups,including single management group (group 1)and systematic management group (group 2 ).During six to twelve months follow －up,the changes in control rate of morning hypertension,serum biochemical indicators,KAP and Mofisky score were observed before and after intervention. Results The proportion of morning hypertension in people with hypertension was 62.25%,61.11% in men and 62.86%in females.The patients with morning hypertension had higher age,BMI,WC,TC,LDL－C,SBP,DBP,CRP, FBG,SCr,Sokolow－Lyon,Cornell,LVMI,UACR and MAU,more cervical plaque,and lower HDL －C and eGFR compared with non－morning hypertension(P＜0.05 －0.001).The number of patients with target organ damage was most in patients with morning hypertension by home blood pressure monitoring(HBPM),second in ambulatory blood pressure monitoring(ABPM),least in clinic blood pressure monitoring (CBPM)(P＜0.05 －0.001).After six to twelve months follow－up,compared with before intervention,the control rate of morning hypertension was increased (43.78%vs.61.39%),and SBP,DBP,HR,BMI,WC,TC,TG,UA,Scr were decreased in both two groups,which in the group 2 were lower than those in the group 1(P＜0.05 ).Compared with before intervention,the KAP score and Mofisky in the two groups after intervention were significantly improved(P＜0.05－0.01)[K score:(9.63 ±3.01)points vs.(14.26 ±2.89)points in the group 1,(10.11±2.34)points vs.(17.23 ±1.06)points in the group2;A score:(2.05 ±1.21)points vs.(2.98 ±0.25)points in the group 1,(2.08 ±1.65)points vs.(3.56 ±0.42)points in the group 2,P score:(4.39 ±2.36)points vs.(5.89 ±3.24)points in the group 1,(4.71±3.42)points vs.(7.26 ± 1.21)points in the group 2,Mofisky questionnaire score:(61.23 ±5.79)points vs.(72.36 ±6.18)points in the group 1,(60.89 ±6.47)points vs.(88.45 ±5.48)points in the group 2],which in the group 2 were higher than those in the group 1(P＜0.01).Conclusion The control rate of morning hypertension in patients with hypertension in Dali Bai autonomous prefecture is low,the HBPM is better way to predict the target organ damage,and systematic management model is effective to improve the control rate of morning hypertension and so do in KAP and Morisky score.

Association of Morning Hypertension Subtype With Vascular Target Organ Damage and Central Hemodynamics.

BACKGROUND: A recent study reported that morning hypertension is associated with poor cardiovascular outcomes in hypertensive patients. However, it is unclear whether morning hypertension associated with sustained nocturnal hypertension and that associated with morning blood pressure (BP) surge differ in terms of their effects on cardiovascular target organ damage and clinical outcomes. The present study aimed to determine the association of morning hypertension with/without nocturnal hypertension with vascular target organ damage and central hemodynamics in patients at high risk for cardiovascular disease. METHODS AND RESULTS: Ambulatory BP monitoring was performed and central BP was measured in 1070 consecutive patients with high cardiovascular risk. We grouped morning hypertension into the following 3 subtypes: (I) morning normotension; (II) morning hypertension without nocturnal hypertension; and (III) morning hypertension with nocturnal hypertension. Morning hypertension was noted in 469 (43.8%) patients and morning hypertension with nocturnal hypertension was noted in 374 (34.9%) patients. The central systolic/diastolic BP and carotid to femoral pulse wave velocity were significantly higher in the subtype III group than in the subtype I and II groups (all P<0.001). Subtype III (versus subtype I) was an independent predictor of central hypertension and high-risk arterial stiffness (P<0.001 and P=0.018, respectively) but not vascular damage in a fully adjusted model (model Y). CONCLUSIONS: Morning hypertension, especially that associated with nocturnal hypertension, is related to high central BP and increased arterial stiffness. Further studies on whether morning hypertension with or without nocturnal hypertension is related to clinical outcomes should be performed. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02003781.

Evidence and Perspectives on the 24-hour Management of Hypertension: Hemodynamic Biomarker-Initiated 'Anticipation Medicine' for Zero Cardiovascular Event.

There are notable differences between Asians and Westerners regarding hypertension (HTN) and the relationship between HTN and cardiovascular disease (CVD). Asians show greater morning surges in blood pressure (BP) and a steeper slope illustrating the link between higher BP and the risk of CVD events. It is thus particularly important for Asian hypertensives to achieve 24-h BP control, including morning and night-time control. There are three components of 'perfect 24-h BP control:' the 24-h BP level, nocturnal BP dipping, and BP variability (BPV), such as the morning BP surge that can be assessed by ambulatory BP monitoring. The morning BP-guided approach using home BP monitoring (HBPM) is the first step toward perfect 24-h BP control, followed by the control of nocturnal HTN. We have been developing new HBPM devices that can measure nocturnal BP. BPV includes different time-phase variability from the shortest beat-by-beat, positional, diurnal, day-by-day, visit-to-visit, seasonal, and yearly changes. The synergistic resonance of each type of BPV would produce a great dynamic BP surge (resonance hypothesis), which triggers a CVD event, especially in the high-risk patients with systemic hemodynamic atherothrombotic syndrome (SHATS). In the future, the innovative management of HTN based on the simultaneous assessment of the resonance of all of the BPV phenotypes using a beat by beat wearable 'surge' BP monitoring device (WSP) and an information and communication technology (ICT)-based data analysis system will produce a paradigm shift from 'dots' BP management to 'seamless' ultimate individualized 'anticipation medication' for reaching a zero CVD event rate.

Coexistence of PM2.5 and low temperature is associated with morning hypertension in hypertensives.

We tested the hypothesis that concentration of PM2.5 is associated with home BP level. We analyzed home BP data for 91 consecutive days in 40 hypertensives. PM2.5 solely was not correlated with home BP levels, but low temperature was associated with a 1.6-fold increased likelihood of morning hypertension (p < 0.001) under the condition of high PM2.5 concentration. In addition, coexistence of low temperature and high PM2.5 was associated with a 2.3-fold increased likelihood of morning hypertension (p < 0.001) compared with high temperature and low PM2.5 condition. Environmental and meteorological factors could be important causes of enhanced home BP elevation.

Benefit of losartan/hydrochlorothiazide-fixed dose combination treatment for isolated morning hypertension: The MAPPY study.

Morning hypertension is an established risk factor for cardiovascular events. In the Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study, a 50-mg losartan/12.5-mg hydrochlorothiazide combination (Los/HCTZ) lowered morning blood pressure (BP) more effectively than 100-mg losartan (High-Los) in treated hypertensive patients with morning hypertension. The aim of this MAPPY study sub-analysis was to determine whether Los/HCTZ was effective for controlling isolated morning hypertension (morning BP ≥ 135/85 mmHg and evening BP < 135/85 mmHg), sustained hypertension (morning and evening BP ≥ 135/85 mmHg), or both. Of the 110 patients studied, 25 (22.7%) had isolated morning hypertension, and 85 (77.3%) had sustained hypertension at baseline. After 3-month treatment, isolated morning hypertension developed into controlled hypertension (morning and evening BP < 135/85 mmHg) in 9 of 11 Los/HCTZ patients (81.8%) and 3 of 14 High-Los patients (21.4%) (p = 0.003, chi-square test). Sustained hypertension developed into controlled hypertension in 21 of 44 Los/HCTZ patients (47.7%) and 13 of 41 High-Los patients (31.7%)(NS). The rates of achievement of SBP < 135 mmHg both in the morning and evening were: 81.8% and 21.4% in Los/HCTZ- and High-Los-treated isolated morning hypertension (p = 0.003), respectively; and 61.4% and 36.6% in Los/HCTX- and High-Los-treated sustained hypertension (p = 0.022), respectively. In conclusion, Los/HCTZ was effective for controlling both types of morning hypertension, especially isolated morning hypertension. Los/HCTZ was superior to High-Los in treating both types of morning hypertension.

Meal-induced blood pressure fall in patients with isolated morning hypertension.

We aimed to determine a possible association between isolated morning hypertension (IMH) and meal-induced blood pressure (BP) fall in adult treated hypertensive patients who underwent home BP measurements. A total of 230 patients were included, median age 73.6, 65.2% women. After adjusting for age, sex, number of antihypertensive drugs, office and home BP levels, the association between IMH and meal-induced BP fall was statistically significant. In conclusion, meal-induced BP fall and IMH detected through home blood pressure monitoring (HBPM) are independently associated in hypertensive patients. The therapeutic implications of such observation need to be clarified in large-scale prospective studies.

Usefulness of morning home blood pressure measurements in patients with type 2 diabetes mellitus: results of a 10-year, prospective, longitudinal study.

Previous cross-sectional studies and 6-year longitudinal study have demonstrated that home blood pressure (HBP) measurements upon awakening have a stronger predictive power for death, micro- and macrovascular complications than clinic blood pressure (CBP) measurements in patients with type 2 diabetes (T2DM). This study investigated which of these measurements offers stronger predictive power for outcomes over 10 years. At baseline, 400 Japanese patients with T2DM were classified as having hypertension (HT) or normotension (NT) based on HBP and CBP. The mean survey duration was 95 months. Primary and secondary end-points were death and new or worsened micro- and macrovascular complications, respectively. Differences in outcomes for each end-point between HT and NT patients were analyzed using Kaplan-Meier survival curves and log-rank testing. Associated risk factors were assessed using Cox proportional hazards analysis. Based on HBP, death and micro- and macrovascular complications were significantly higher in patients with HT than with NT at baseline and end-point. Based on CBP, there were no significant differences in incidence of death, micro- or macrovascular complications between patients with HT and NT at baseline and end-point, although a significant difference in incidence of death was observed between the HT and NT groups at end-point. However, the significance was significantly lower in CBP than in HBP. One risk factor associated with micro- and macrovascular complications in patients with HBP was therapy for HT. This 10-year longitudinal study of patients with T2DM demonstrated that elevated HBP upon awakening is predictive of death, and micro- and macrovascular complications.

Diabetes and obesity are significant risk factors for morning hypertension: from Ibaraki Hypertension Assessment Trial (I-HAT).

AIMS: Although morning hypertension (HT) has been identified as a major cardiovascular risk, susceptible populations remain unknown. This study aimed to clarify the relationship between morning HT and diabetes or obesity in a large-scale population. MAIN METHODS: Clinic blood pressure (BP) and BP upon awakening were recorded in 2554 outpatients with HT who attended 101 clinics or hospitals for two weeks. Mean clinic and awakening BP>140/90 and >135/85 mmHg, respectively, were considered as HT. The patients were classified according to values for clinic and home BP, into normal BP, white coat HT, masked HT, and sustained HT. KEY FINDINGS: Morning BP (mmHg) significantly and progressively elevated in the order of normal glucose tolerance, impaired glucose tolerance and diabetes (134.1 ± 12.2, 135.4 ± 13.1 and 137.5 ± 11.5; p<0.0001). The incidence of morning HT significantly increased and progressively in the same order (53.4%, 55.6%, 66.4%, p<0.0001). Morning BP was significantly higher among obese patients with diabetes than among non-obese and non-diabetic patients (138.8 ± 10.5, 133.1 ± 11.9, p<0.0001). In addition, the incidence of morning HT was significantly higher in obese diabetic patients than in non-obese and non-diabetic patients (73.0% vs. 49.9%, p<0.0001). SIGNIFICANCE: Diabetic or obese patients frequently have morning HT.

Efficacies of Controlling Morning Blood Pressure and Protecting the Kidneys by Treatment With Valsartan and Nifedipine CR or Valsartan and Amlodipine (MONICA Study).

BACKGROUND: It is controversial whether a single-pill fixed-dose combination of angiotensin II type 1 receptor blocker and calcium channel blocker (CCB) is effective for all types of hypertension. METHODS: Thirty-five patients with uncontrolled blood pressure (BP) under treatment with valsartan 80 mg/day or amlodipine 5 mg/day were enrolled. They were randomly divided into two treatment groups: a single-pill fixed-dose combination of valsartan 80 mg/day and amlodipine 5 mg/day in the morning (VA group), or valsartan 80 mg/day in the morning and nifedipine CR 20 mg/day at night (VN group), and treated for 16 weeks. If the patient did not reach the target office BP at 8 weeks, they received double doses of CCBs. RESULTS: In the VN group, morning diastolic BP was significantly lower than the respective values in the VA group at 8 weeks. The percentage of patients who required a double dose of CCB in the VN group was significantly lower than that in the VA group. At 16 weeks, the BP levels in both groups were significantly reduced. Urinary albumin/creatinine at 16 weeks was significantly less than that at 0 weeks in the VN group. CONCLUSION: Combination therapy with valsartan and nifedipine CR may help to control morning BP and protect the kidneys.

A New Baroreceptor Sensitivity-Restoring Ca-Channel Blocker Diminishes Age-Related Morning Blood Pressure Increase in Hypertensive Patients: Open-Label Monitoring of Azelnidipine Treatment for Hypertension in the Early Morning (At-HOME) Study.

BACKGROUND: Morning blood pressure (BP) surge, which exhibits an age-related increase, is a risk factor for stroke in elderly hypertensive patients, independently of the 24-h BP level. We studied the effect of the new baroreceptor sensitivity (BRS)-restoring Ca-channel blocker (CCB) azelnidipine (AZ) on this age-related morning BP increase. METHODS: We conducted a 16-week prospective study to clarify the effect of morning dosing of AZ on home BPs measured in the morning and in the evening in 2,546 hypertensive patients (mean age, 65.1 years; female, 53.6%). RESULTS: At baseline, ME-Dif (morning systolic BP [SBP]-evening SBP) increased with age, independently of ME-Ave (average of the morning and evening SBPs). This age-related increase of ME-Dif was exaggerated by regular alcohol drinking and beta-blocker use. After AZ treatment (14.3 ± 3.6 mg/day), ME-AV and ME-Dif were significantly reduced independently of each other, with reductions of -18.1 ± 15.6 and -2.5 ± 13.2 mmHg, respectively (both p < 0.001). AZ treatment decreased age-related increase in ME-Dif particularly in patients who were regular consumers of alcohol and in beta-blocker users. CONCLUSIONS: The new BRS-restoring CCB AZ significantly reduced age-related increase in morning BP and had some potential benefit on cardiovascular protection in hypertension, particularly in elderly patients and/or consumers of alcohol.