Yasuyuki Okuda

Increased cardiovascular risk of treated white coat and masked hypertension in patients with diabetes and chronic kidney disease: the HONEST Study

The prognostic implications of treated white coat hypertension (WCH) and masked hypertension (MH) in patients with diabetes mellitus (DM) or chronic kidney disease (CKD) are not well documented. Using data from the HONEST study (n=21 591), we investigated the relationships between morning home systolic blood pressure (MHSBP) or clinic systolic blood pressure (CSBP) and cardiovascular (CV) risk in hypertensive patients with and without DM or CKD receiving olmesartan-based antihypertensive therapy. The study included 4426 DM patients and 4346 CKD patients at baseline who had 101 and 87 major CV events, respectively, during the follow-up. Compared with well-controlled non-DM patients (MHSBP <135 mm Hg; CSBP <140 mm Hg), DM patients with WCH (MHSBP <135 mm Hg; CSBP ⩾140 mm Hg), MH (MHSBP ⩾135 mm Hg; CSBP <140 mm Hg) or poorly controlled hypertension (PCH) (MHSBP ⩾135 mm Hg; CSBP ⩾140 mm Hg) had significantly higher CV risk (hazard ratio (HR), 2.73, 2.77 and 2.81, respectively). CV risk was also significantly increased in CKD patients with WCH, MH and PCH (HR, 2.14, 1.70 and 2.20, respectively) compared with well-controlled non-CKD patients. Furthermore, DM patients had significantly higher incidence rate than non-DM patients of MHSBP ⩾125 to <135 mm Hg (HR, 1.98) and ⩾135 to <145 mm Hg (HR, 2.41). In conclusion, both WCH and MH are associated with increased CV risk, and thus control of both MHSBP and CSBP is important to reduce CV risk in DM or CKD patients. The results also suggest that even lower MHSBP (<125 mm Hg) may be beneficial for DM patients, although this conclusion is limited by the small number of patients.

Lipid and blood pressure control for the prevention of cardiovascular disease in hypertensive patients: a subanalysis of the OMEGA study.

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.

Dynamic prediction model and risk assessment chart for cardiovascular disease based on on-treatment blood pressure and baseline risk factors

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.

Risk factors for primary prevention of cardiovascular disease and risk reduction by lipid control: the OMEGA study risk factor sub-analysis.

Abstract To identify risk factors for cardiovascular disease (CVD) in hypertensive patients with no history of CVD being treated with antihypertensive drugs, we examined subgroup data (n = 13 052) from the prospective, observational Olmesartan Mega Study to Determine the Relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement (OMEGA) study. Risk factors for CVD, stroke and coronary heart disease (CHD) were examined using a Cox proportional hazards model. In addition, the effect of statin therapy at baseline on CHD prevention was analyzed in dyslipidemic patients. The factors significantly related to CVD were female (hazard ratio [HR] = 0.637, 95% confidence interval [CI] 0.428–0.948), older age (65–69 years: HR = 2.165, 95% CI 1.214–3.861; 70–74 years: HR = 2.324, 95% CI 1.294–4.174; ≥75 years: HR = 2.448, 95% CI 1.309–4.578), family history of CHD (HR = 1.993, 95% CI 1.249–3.179), diabetes (HR = 2.287, 95% CI 1.700–3.078), current smoking (HR = 2.289, 95% CI 1.512–3.466) and alcohol drinking socially (HR = 0.589, 95% CI 0.379–0.913). Diabetes was a risk factor for both stroke and CHD, while age, family history of CHD, and sodium intake score were risk factors for stroke alone. Sex, dyslipidemia, smoking and exercise habits were risk factors for CHD alone. The risk of CHD in dyslipidemic patients on statin treatment was comparable to the risk in patients without dyslipidemia (HR = 1.134, 95% CI 0.604–2.126). However, in dyslipidemic patients not on statin treatment, the HR increased to 1.807 (95% CI 1.156–2.825). In conclusion, some risk factors for CVD in hypertensive patients being treated with antihypertensive drugs with no history of CVD differed between CHD and stroke. These results suggest the importance of managing dyslipidemia with a statin for primary prevention of CHD, as well as the importance of hypertension therapy.

Prognostic significance of on-treatment home and clinic blood pressure for predicting cardiovascular events in hypertensive patients in the HONEST study.

Objective: We investigated the prognostic significance of morning home SBP (MHSBP) and clinic SBP (CSBP) at baseline and during follow-up in on-treatment hypertensive patients. Methods: In the Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure study, more than 20 000 Japanese hypertensive patients who started treatment with olmesartan were followed for cardiovascular events for 2 years. MHSBP and CSBP measured at baseline and during follow-up were compared in terms of the prognostic significance in predicting cardiovascular events. Results: The analysis included 21 591 patients (50.6% female; average age 64.9 years; mean follow-up 2.02 years; and 280 cardiovascular events). The mean MHSBP and CSBP were 151.2 and 153.6 mmHg at baseline and 135.2 and 135.2 mmHg during follow-up. Hazard ratios per 1 mmHg increase were 1.011 (95% confidence interval 1.004–1.019) and 1.006 (1.000–1.012) at baseline, and 1.039 (1.029–1.049) and 1.026 (1.016–1.036) during follow-up. When MHSBP and CSBP at baseline and during follow-up were included in the same model, only MHSBP during follow-up was identified as a significant predictive factor. The concordance index of all blood pressure variables showed reasonable discrimination abilities, and that of mean during follow-up were higher than that of SBP at baseline. The results of net reclassification improvement analyses showed that follow-up MHSBP had better reclassification ability than follow-up CSBP. Conclusion: SBP during follow-up (as compared with SBP at baseline), particularly MHSBP (as compared with CSBP), had better prognostic significance in predicting cardiovascular events in Japanese hypertensive patients during a 2-year clinical study.

Persistent olmesartan-based blood pressure-lowering effects on morning hypertension in Asians: the HONEST study.

Using data from the large-scale HONEST (Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure) study, we investigated the characteristics of the effects of olmesartan-based treatment on morning hypertension in Asian hypertensive patients. Specifically, we investigated the relationship between baseline blood pressure (BP) and BP reduction after 16 weeks by linear regression analyses; determinants of BP reduction were also investigated. For both morning home BP (MHBP) and clinic BP (CBP), reduced systolic BP (SBP) after 16 weeks was associated with baseline SBP (P<0.001). The slope of the regression lines was similar for morning home SBP (MHSBP) (−0.744) and clinic SBP (−0.735). Although sex, concomitant diabetes mellitus and concomitant hepatic disease significantly influence the relationship between BP reduction and baseline BP for MHSBP, none were deemed clinically relevant. In conclusion, olmesartan-based treatment robustly reduced baseline high MHBP, similar to CBP, and the effect was associated with baseline BP but unaffected by patient background factors.

Home blood pressure and cardiovascular risk in treated hypertensive patients: the prognostic value of the first and second measurements and the difference between them in the HONEST study

Hypertension guidelines recommend using the average of two home blood pressure (HBP) measurements obtained on one occasion to monitor blood pressure. We studied the prognostic value of the first and second measurements or their average value during the follow-up period, as well as the relationships among the difference between the first and second HBP measurements and the prognosis using data from the HONEST (HBP measurement with Olmesartan-Naive patients to Establish Standard Target blood pressure) study. During the mean 2.02 years follow-up, 280 patients had cardiovascular events. Hazard ratios (HRs) for cardiovascular events for each 1 mm Hg increase in the first, second and averaged morning home systolic blood pressure (MHSBP) were similar. Hazards were significantly higher in patients with a large difference between the first and second MHSBP (ΔMHSBP) of <−5 mm Hg (HR: 2.12) or ⩾5 mm Hg (HR: 1.44) compared with those with a small ΔMHSBP of ⩾−5 to <5 mm Hg using the Cox proportional hazards model adjusted for the averaged MHSBP during the follow-up and other risk factors. Hazards in patients with an averaged MHSBP ⩾145 mmHg and a small ΔMHSBP (HR: 3.11), those with an averaged MHSBP ⩾125 to <145 mm Hg and a large ΔMHSBP (HR: 1.91) and those with an averaged MHSBP ⩾145 mm Hg and a large ΔMHSBP (HR: 4.63) were higher compared with those with an averaged MHSBP <125 mm Hg and a small ΔMHSBP. In conclusion, the first, second and averaged MHSBP measurements have similar prognostic values. Prognosis is worse for patients with a large ΔMHSBP. In clinical practice, it would be prudent to measure the HBP two times and use the average HBP of two measurements obtained on one occasion with particular attention to patients with a large ΔMHSBP.

Effectiveness of olmesartan-based treatment on home and clinic blood pressure in elderly patients with masked and white coat hypertension

Few large-scale studies have evaluated the effectiveness of angiotensin receptor blockers in patients with masked hypertension (MH) and white coat hypertension (WCH) based on age using real-world blood pressure (BP) data. We used data from the Home BP measurement with Olmesartan Naive patients to Establish Standard Target BP (HONEST) study to investigate the effectiveness of olmesartan-based treatment by patient age (<65 years of age, n=9817; 65–74 years of age, n=6792; ⩾75 years of age, n=4732), focusing on morning home BP (strongly associated with cardiovascular disease and useful for MH and WCH diagnosis). Sixteen weeks of treatment changed morning home BP (mean systolic/diastolic) by −18.1/−9.7, −15.9/−7.4 and −14.2/−6.4 mm Hg and clinic BP by −20.1/−11.3, −17.3/−8.7 and −15.4/−7.2 mm Hg, in these age groups, respectively (P<0.0001). Pulse pressure decreased (−7.8 to −8.8 mm Hg, P<0.0001). Patients aged ⩾80 years experienced similar BP and pulse pressure changes. In patients aged ⩾75 years, mean morning and clinic BP after 16 weeks was 137.5/74.8 and 129.7/70.4 mm Hg, respectively, in MH patients and 132.3/72.2 and 139.7/72.7 mm Hg, respectively, in WCH patients. Regardless of age, only elevated clinic or home BP values decreased to target ranges. The incidence of adverse effects associated with excessive BP lowering was low in all of the age groups. In conclusion, our study suggests that olmesartan-based treatment was safe and useful for managing MH, WCH and sustained hypertension in elderly patients. The lack of a placebo group was a limitation of the study.

Home blood pressure and cardiovascular outcomes in very elderly patients receiving antihypertensive drug therapy: a subgroup analysis of Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure (HONEST) study

ABSTRACT The appropriate target blood pressure (BP) in elderly patients with hypertension remains uncertain. We investigated the relationship between morning home systolic blood pressure (MHSBP) during follow-up and cardiovascular (CV) risk in outpatients receiving olmesartan-based treatment aged <75 years (n = 16799) and ≥75 years (n = 4792) in the HONEST study. In the follow-up period (mean 2.02 years), the risk for major CV events was significantly higher in patients with MHSBP ≥155 mmHg compared with <125 mmHg in both age groups in Cox proportional hazards model adjusted for other risk factors and there was no significant difference in trend between the two groups (interaction P = 0.9917 for MHSBP). Hazard ratios for CV events for 1-mmHg increase in MHSBP were similar in patients aged <75 years and in patients aged ≥75 years. The incidence of adverse drug reactions related to excessive BP lowering was lower in patients <75 years than in patients ≥75 years (0.73 vs 1.02%, P = 0.0461). In conclusion, the study suggests even in patients ≥75 years antihypertensive treatment targeting the same MHSBP levels in patients <75 years may be beneficial in reducing CV risk when treatment is tolerated.

LB01.02: MORNING HOME BLOOD PRESSURE IS A STRONG PREDICTOR OF CORONARY ARTERY DISEASE EVENTS AS WELL AS STROKE EVENTS IN HYPERTENSIVE PATIENTS ON ANTIHYPERTENSIVE TREATMENT. THE HONEST STUDY.

Objective: Previous studies indicated that clinic blood pressure (CBP) is a strong predictor of stroke events, but CBP does not predict coronary artery disease (CAD) events so strongly. Morning home blood pressure (HBP) is more closely associated with stroke risk than CBP. However, few studies have investigated the relationship between morning HBP and CAD risk. We investigated the relationship between morning HBP and incidence of stroke events and CAD events, respectively, using data from the HONEST study. Design and method: HONEST was a prospective observational study of hypertensive outpatients on olmesartan-based antihypertensive treatment. All the ischemic and hemorrhagic cerebrovascular events expect transient ischemic attack were defined as stroke events, and myocardial infarction and angina pectoris with coronary revascularization procedure were defined as CAD events. Results: In 21591 participants (mean age, 64.9 years; mean follow-up, 2.02 years), 127 (2.92/1000 patient years) stroke events and 121 (2.78/1000 patient years) CAD events occurred. The incidence of stroke events was significantly increased in morning HBP >=145 to <155 mmHg and >=155 mmHg compared with <125 mmHg; also in CBP >=150 to <160 mmHg and >=160 mmHg compared with <130 mmHg. The hazard ratio (HR) in morning HBP >155 mmHg was 6.01 (95% CI, 2.85–12.68) compared with <125 mmHg; in CBP >=160 mmHg, it was 5.82 (3.17–10.67) compared with <130 mmHg, indicating that morning HBP predicted stroke events similarly to CBP. The incidence of CAD events was significantly increased in morning HBP>=145 to <155 mmHg and >=155 mmHg compared with <125 mmHg; in CBP >=160 mmHg compared with <130 mmHg, but not in CBP >=150 to <160 mmHg. The HR in morning HBP >=155 mmHg was 6.24 (2.82–13.84). In contrast, the HR in CBP >=160 mmHg was 3.51 (1.71–7.20), indicating that CBP underestimated CAD risk compared to morning HBP. Conclusions: Morning HBP predicted CAD events similarly to stroke events. In contrast, CBP is more likely to underestimate CAD risk than morning HBP. Morning SBP-guided approach for managing hypertension may be more effective in predicting future risk of CAD events than CBP-based one.