• María T Ríos, Manuel Domínguez-Sardiña, Diana E Ayala, Sonia Gomara, Elvira Sineiro, Lorenzo Pousa, Pedro A Callejas, María J Fontao, José R Fernández, Ramón C Hermida, and Hygia Project Investigators.
• Bioengineering and Chronobiology Laboratories University of Vigo, Campus Universitario, Vigo, Pontevedra, Spain.
• Chronobiol. Int. 2013 Mar 1;30(1-2):207-20.

AbstractHypertension is defined as resistant to treatment when a therapeutic plan including ≥3 hypertension medications failed to sufficiently lower systolic (SBP) and diastolic (DBP) blood pressures (BPs). Most individuals, including those under hypertension therapy, show a "white-coat" effect that could cause an overestimation of their real BP. The prevalence and clinical characteristics of "white-coat" or isolated-office resistant hypertension (RH) has always been evaluated by comparing clinic BP values with either daytime home BP measurements or the awake BP mean obtained from ambulatory monitoring (ABPM), therefore including patients with either normal or elevated asleep BP mean. Here, we investigated the impact of including asleep BP mean as a requirement for the definition of hypertension on the prevalence, clinical characteristics, and estimated cardiovascular (CVD) risk of isolated-office RH. This cross-sectional study evaluated 3042 patients treated with ≥3 hypertension medications and evaluated by 48-h ABPM (1707 men/1335 women), 64.2 ± 11.6 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 522 (17.2%) had true isolated-office RH (elevated clinic BP and controlled awake and asleep ambulatory BPs while treated with 3 hypertension medications), 260 (8.6%) had false isolated-office RH (elevated clinic BP, controlled awake SBP/DBP means, but elevated asleep SBP or DBP mean while treated with 3 hypertension medications), and the remaining 2260 (74.3%) had true RH (elevated awake or asleep SBP/DBP means while treated with 3 medications, or any patient treated with ≥4 medications). Patients with false, relative to those with true, isolated-office RH had higher prevalence of microalbuminuria and chronic kidney disease (CKD), significantly higher albumin/creatinine ratio (p < .001), significantly higher 48-h SBP/DBP means by 9.6/5.3 mm Hg (p < .001), significantly lower sleep-time relative SBP and DBP decline (p < .001), and significantly greater prevalence of a non-dipper BP profile (96.9% vs. 38.9%; p < .001). Additionally, the prevalence of the riser BP pattern, which is associated with highest CVD risk, was much greater, 40.4% vs. 5.0% (p < .001), among patients with false isolated-office RH. The estimated hazard ratio of CVD events, using a fully adjusted model including the significant confounding variables of sex, age, diabetes, chronic kidney disease, asleep SBP mean, and sleep-time relative SBP decline, was significantly greater for patients with false compared with those with true isolated-office RH (2.13 [95% confidence interval: 1.95-2.32]; p < .001). Patients with false isolated-office hypertension and true RH, however, were equivalent for the prevalence of obstructive sleep apnea, metabolic syndrome, obesity, diabetes, microalbuminuria, and chronic kidney disease, and they had an equivalent estimated hazard ratio of CVD events (1.04 [95% confidence interval: .97-1.12]; p = .265). Our findings document a significantly elevated prevalence of a blunted nighttime BP decline in patients here categorized as either false isolated-office RH and true RH, jointly accounting for 82.8% of the studied sample. Previous reports of much lower prevalence of true RH plus a nonsignificant increased CVD risk of this condition compared with isolated-office RH are misleading by disregarding asleep BP mean for classification. Our results further indicate that classification of RH patients into categories of isolated-office RH, masked RH, and true RH cannot be based on the comparison of clinic BP with either daytime home BP measurements or awake BP mean from ABPM, as so far customary in the available literature, totally disregarding the highly significant prognostic value of nighttime BP. Accordingly, ABPM should be regarded as a clinical requirement for proper diagnosis of true RH.

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