BackgroundMorning hypertension is a risk factor for cardiovascular and cerebrovascular events. Furthermore, it is a useful measure for definitive diagnosis of hypertension, and patients who self-assess their own blood pressure (BP) in the morning tend to exhibit better compliance with antihypertensive medication than those who do not.ObjectiveThe objective of this analysis was to determine the BP- and pulse rate-lowering effects of azelnidipine, a long-acting dihydropyridine calcium antagonist administered once daily in the morning.MethodsWe conducted the Azelnidipine Treatment for Hypertension Open-label Monitoring in the Early morning (At-HOME) Study by surveying patients who were taking azelnidipine. According to the study protocol, high systolic BP (SBP) was defined as ≥135 mmHg when measured at home in the morning and ≥140 mmHg when measured at the clinic during the day. A total of 5,433 hypertensive patients, who were registered at 1,011 medical institutions across Japan, were enrolled in the study. Data obtained from 4,852 of these patients (mean age, 64.8 years; female, 52.9 %; previous medication with other antihypertensive agents used concomitantly with the present study agent, 45.5 %) were used for efficacy analysis.ResultsAt baseline, the subjects’ mean [± standard deviation] SBP/diastolic BP values at home in the morning, at the clinic during the day, and at home in the evening were 156.9 ± 16.4/89.7 ± 12.0, 157.5 ± 18.7/89.1 ± 13.3, and 150.2 ± 17.6/85.6 ± 12.2 mmHg, respectively. The mean pulse rates were 72.7 ± 10.7, 74.9 ± 11.2, and 72.5 ± 9.6 beats/min, respectively. Patients whose BP was defined as high accounted for 83.4 % of the study population, whereas 9.9 % had ‘masked’ hypertension, defined as SBP of ≥135 mmHg at home in the morning and <140 mmHg at the clinic. However, from 4 weeks after initiation of azelnidipine treatment till the end of the study at week 16, all three daily BP determinations were significantly (p < 0.0001) lowered, and pulse rates at home in the morning, at the clinic, and at home in the evening were similarly and significantly reduced (by −3.7 ± 8.0, −3.5 ± 9.5, and −3.5 ± 7.3 beats/min, respectively). Whereas achievement of home SBP of <135 mmHg in the morning was noted in only 6.6 % of patients before the start of azelnidipine treatment, this was noted in 43.3 % after 16 weeks. Meanwhile, achievement of clinic SBP of <140 mmHg was increased from 12.9 % of patients to 56.1 % of patients at the same timepoints. After azelnidipine treatment, 32.2 % of patients had well-controlled hypertension in both the home and clinic settings. Adverse drug reactions occurred in 2.92 % of patients (154/5,265). All adverse drug reactions were as expected for the calcium antagonist class of agents.ConclusionThese data suggest that azelnidipine controlled morning hypertension well. Furthermore, azelnidipine reduced pulse rates significantly.Electronic supplementary materialThe online version of this article (doi:10.1007/s40268-013-0006-8) contains supplementary material, which is avail...

For patients with hypertension, an individual risk prediction tool for cardiovascular disease based on on-treatment blood pressure is needed and would be useful. The objective of this study was to establish a 3-year risk prediction model for cardiovascular disease based on data from 13 052 patients with no history of cardiovascular disease in the Olmesartan Mega study to determine the relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement study. To develop dynamic prediction models including on-treatment blood pressure, a Cox proportional hazard model using the sliding landmarking method with three landmark points (6, 12 and 18 months from baseline) was used. The prediction model included blood pressure (<130/85 mm Hg, ⩾130/85  to <140/90 mm Hg, ⩾140/90 to <160/100 mm Hg and ⩾160/100 mm Hg) as a time-dependent covariate and well-known baseline risk factors (sex, age, smoking, family history of coronary artery disease and diabetes) as covariates. The 3-year risk assessment chart was constructed using the combination of all risk factors in the prediction model, and six different colors were displayed on each chart corresponding to the predicted probability of cardiovascular disease. Judging from the chart, if an elderly man with diabetes and other risk factors had a blood pressure of <130/85 mm Hg at 6 months, the risk of cardiovascular disease would be 8.0%, whereas the risk would be 8.6% if he had a blood pressure of ⩾130/85 to <140/90 mm Hg. The risk assessment chart developed from the large-scale observational study data would help physicians to more easily assess the cardiovascular disease risk for hypertensive patients on antihypertensive treatments.

Aim:The aim of this analysis was to investigate the relationships between dyslipidemia, achieved blood pressure (BP) values and the lipid levels, as well as the control of four cardiovascular risk factors (BP, low-density lipoprotein: LDL cholesterol, hemoglobin A1c: HbA1c and smoking) and the incidence of cardiovascular disease (CVD), in Japanese patients receiving antihypertensive therapy. Methods: A total of 13,052 patients with no history of CVD were included in this subanalysis of the prospective observational OMEGA study in Japanese hypertensive patients treated with olmesartan. Multivariable Cox regression models were used to evaluate the relationship with the risk of CVD. Results: The incidence of CVD during the 36-month study period was 5.59/1,000 patient-years among the patients with dyslipidemia (n 6,297) and 5.57/1,000 patient-years among the patients without dyslipidemia (n 6,755), with no significant differences between the two groups. Higher achieved BP values tended to be associated with an increased CVD risk in both the patients with and without dyslipidemia. In addition, the risk of CVD tended to be higher in the patients with an achieved LDL cholesterol level of ≥ 120 mg/dL than in those with an LDL level of 120 mg/dL (trend p 0.0005) and in the patients with an achieved high-density lipoprotein cholesterol level of 60 mg/dL than in those with an HDL level of ≥ 60 mg/dL (trend p 0.0017). Furthermore, the risk of CVD was higher among the patients with fewer controlled risk factors than among those with control of all four risk factors (trend p 0.0001). Conclusions: In order to prevent CVD in olmesartan-treated hypertensive patients with no history of CVD, it is important to control both the lipid and BP levels and aim for comprehensive risk factor control.J Atheroscler Thromb, 2015; 22:62-75.

We investigated the relationship between cardiovascular disease (CVD) and the achieved blood pressure, dietary habits and the presence/absence of metabolic syndrome (MetS) in hypertensive patients treated with olmesartan medoxomil. A prospective cohort study with a 3-year follow-up was conducted in 14 721 olmesartan-naive outpatients (mean age: 64.9 years, 49.6% women) with essential hypertension. The association of CVD with achieved blood pressure, dietary habits and MetS was investigated by Cox proportional hazards analysis. There were 3059 patients (31.8%) with MetS (Japanese criteria) among 9625 evaluable patients. The mean baseline blood pressure was 157.4/88.8 mm Hg, which decreased to 134.0/76.1 mm Hg during treatment (P<0.0001). The annual incidence of CVD was 7.15 per 1000 persons during the study period. When the achieved blood pressure was stratified according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009), the risk of CVD increased significantly along with the severity of hypertension (P<0.0001), especially the risk of stroke. Investigation of dietary habits revealed a significant association between salt intake and the risk of stroke. Higher salt intake was associated with a significantly higher risk of stroke than lower salt intake (hazard ratio, 1.897; 95% confidence interval, 1.003–3.590). Blood pressure was well controlled in both patients with and without MetS, and there was no significant difference in the incidence of events between the two groups. In conclusion, the severity of hypertension (achieved blood pressure) is associated with the incidence of CVD, and the results of this study suggest that tight blood pressure control and salt restriction are important for preventing stroke.

BackgroundMorning hypertension is a risk factor for cardiovascular and cerebrovascular events, and consequently diagnosis and control of morning hypertension are considered very important. We previously reported the results of the Azelnidipine Treatment for Hypertension Open-label Monitoring in the Early morning (At-HOME) Study, which indicated that azelnidipine effectively controlled morning hypertension.ObjectivesThe objective of this At-HOME subgroup analysis was to evaluate the sustained blood pressure (BP)-lowering effect of azelnidipine, using mean morning and evening systolic BP [ME average] and morning systolic BP minus evening systolic BP (ME difference).MethodsWe analyzed the self-measured home BP data (measured in the morning and at bedtime) from this 16-week prospective observational study to clarify the effect of morning dosing of azelnidipine (mean [± standard deviation] maximum dose 14.3 ± 3.6 mg/day). A subgroup of patients from the At-HOME Study who had an evening home BP measurement within 28 days prior to the baseline date were used for efficacy analysis (n = 2,546; mean age, 65.1 years; female, 53.6 %).ResultsHome systolic BP/diastolic BP levels in the morning and evening were significantly lowered (p < 0.0001) by −19.4 ± 17.1/−10.3 ± 10.6 and −16.9 ± 17.0/−9.4 ± 10.6 mmHg, respectively. Home pulse rates in the morning and evening were also significantly lowered (p < 0.0001) by −3.5 ± 7.8 and −3.5 ± 7.3 beats/min, respectively. At baseline, patients whose ME average was ≥135 mmHg and whose ME difference was ≥15 mmHg (defined as morning-predominant hypertension) accounted for 20.4 % of the study population. However, at the end of the study, the number of such patients was significantly reduced to 7.9 % (p < 0.0001). Patients whose ME average was ≥135 mmHg and whose ME difference was <15 mmHg (defined as sustained hypertension) accounted for 71.1 % of the study population at baseline. This was reduced significantly to 42.8 % at the end of the study (p < 0.0001). ME average decreased significantly from 153.8 ± 15.5 mmHg to 135.6 ± 11.9 mmHg, and ME difference also decreased significantly from 6.7 ± 13.1 mmHg to 4.7 ± 10.8 mmHg (both p < 0.0001).ConclusionThese results suggest that azelnidipine improved morning hypertension with its sustained BP-lowering effect.Electronic supplementary materialThe online version of this article (doi:10.1007/s40268-013-0007-7) contains supplementary material, which is available to authorized users.