Prognostic value of non‐resistant and resistant masked uncontrolled hypertension detected by ambulatory blood pressure monitoring

Abstract Masked uncontrolled hypertension (MUCH) is at higher cardiovascular risk than controlled hypertension (CH). In previous studies, patients with MUCH were considered as a unique group though those receiving ≤2 drugs could be defined as having nonresistant MUCH (NRMUCH) and those receiving ≥3 drugs as having resistant MUCH (RMUCH). The aim of this study was to assess the prognostic value of NRMUCH and RMUCH detected by ambulatory blood pressure (BP) monitoring. Cardiovascular risk was evaluated in 738 treated hypertensive patients with normal clinic BP. Patients were classified as having CH or MUCH if daytime BP < or ≥ 135/85 mmHg, respectively, regardless of nighttime BP, or CH or MUCH if 24‐h BP < or ≥ 130/80 mmHg, respectively, regardless of daytime or nighttime BP. By daytime or 24‐h BP, the authors detected 523 (71%), 178 (24%), and 37 (5%) or 463 (63%), 231 (31%), and 44 (6%) patients with CH, NRMUCH, and RMUCH, respectively. During the follow‐up (median 10 years), 148 events occurred. After adjustment for covariates, compared to CH, the hazard ratio (HR), 95% confidence interval (CI), for cardiovascular events was 1.81, 1.27–2.57, and 2.99, 1.73–5.16, in NRMUCH and RMUCH defined by daytime BP, respectively, and 1.58, 1.12–2.23, and 2.21, 1.27–3.82, in NRMUCH and RMUCH defined by 24‐h BP, respectively. If RMUCH was compared with NRMUCH, the risk tended to be higher in RMUCH but did not attain statistical significance (P = .08 and P = .23 by daytime and 24‐h BP thresholds, respectively). In conclusion, both NRMUCH and RMUCH are at increased cardiovascular risk than CH.

The aim of this study was to evaluate the prognostic value of NRMUCH and RMUCH detected by ambulatory BP monitoring.

Patients
We studied 738 treated hypertensive patients with normal clinic BP selected from 2264 sequential treated individuals aged 30

Echocardiography
Patients underwent a comprehensive echocardiographic investigation, which included two-dimensional, M-mode, and Doppler examinations.
Left atrial (LA) and left ventricular (LV) measurements and calculation of LV mass were made according to standardized methods. 22

Follow-up
Patients were followed-up in our outpatient clinic or by their family doctors. The occurrence of events was recorded during follow-up visits or by telephone interview of the family doctor or the patient or a family member, followed by a visit if the patient was alive. Medical records were obtained to confirm the events. We evaluated a combined endpoint including coronary events (sudden death, fatal and nonfatal myocardial infarction, and coronary revascularization), fatal and nonfatal stroke, heart failure requiring hospitalization and peripheral revascularization. Outcomes were defined according to standard criteria as previously reported. 24-28
variables. Event rates were expressed as the number of events per 100 patient-years. Survival curves were estimated using the Kaplan-Meier Nighttime systolic BP tended to be higher, but did not attain statistical significance, in patients with RMUCH (P = .07 and P = .12 for daytime and 24-h definitions, respectively).
Antihypertensive therapy is shown in  (Figure 1). Survival curves are reported in Figure 2.
Results of univariate and multivariate Cox regression analyses are reported in Table 4 Table 2).
When study groups were defined according to nighttime BP threshold (120/70 mmHg) regardless of daytime BP, RMUCH was not at significantly higher risk than CH and it was at slightly higher risk than NRMUCH (Supplemental Table 3). When CH, NRMUCH and RMUCH were defined by both daytime and nighttime BP thresholds, results tended to be similar to those obtained by using daytime BP threshold regardless of nighttime BP (Supplemental Table 3).

DISCUSSION
The present study shows that both NRMUCH and RMUCH are at increased cardiovascular risk than CH.
Previous studies showing higher cardiovascular risk in patients with MUCH than in those with CH have analyzed the MUCH group as a unique entity. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] At present, to the best of our knowledge, only one study has evaluated the prognostic value of RMUCH. 19  In conclusion, our study shows that both NRMUCH and RMUCH are at increased cardiovascular risk than CH. In this context, our data suggest that therapeutic strategy should be specifically addressed in patients with NRMUCH and RMUCH for a better reduction of cardiovascular risk.