Lorenzo Pousa

Prevalence and Clinical Characteristics of Isolated-Office and True Resistant Hypertension Determined by Ambulatory Blood Pressure Monitoring

Hypertension 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. (Author correspondence: rhermida@uvigo.es)

Effects of Time-of-Day of Hypertension Treatment on Ambulatory Blood Pressure and Clinical Characteristics of Patients With Type 2 Diabetes

Generally, hypertensive patients ingest all their blood pressure (BP)-lowering agents in the morning. However, many published prospective trials have reported clinically meaningful morning-evening, treatment-time differences in BP-lowering efficacy, duration of action, and safety of most classes of hypertension medications, and it was recently documented that routine ingestion of ≥1 hypertension medications at bedtime, compared with ingestion of all of them upon awakening, significantly reduces cardiovascular disease (CVD) events. Non-dipping (<10% decline in asleep relative to awake BP mean), as determined by ambulatory BP monitoring (ABPM), is frequent in diabetes and is associated with increased CVD risk. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and analytical parameters of hypertensive patients with type 2 diabetes evaluated by 48-h ABPM. This cross-sectional study involved 2429 such patients (1465 men/964 women), 65.9 ± 10.6 (mean ± SD) yrs of age, enrolled in the Hygia Project, involving primary care centers of northwest Spain and designed to evaluate prospectively CVD risk by ABPM. Among the participants, 1176 were ingesting all BP-lowering medications upon awakening, whereas 1253 patients were ingesting ≥1 medications at bedtime. Among the latter, 336 patients were ingesting all BP-lowering medications at bedtime, whereas 917 were ingesting the full daily dose of some hypertension medications upon awakening and the full dose of others at bedtime. Those ingesting ≥1 medications at bedtime versus those ingesting all medications upon awakening had lower likelihood of metabolic syndrome and chronic kidney disease (CKD); had significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; and had higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. Moreover, patients ingesting all medications at bedtime had lowest fasting glucose, serum creatinine, uric acid, and prevalence of proteinuria and CKD. Ingestion of ≥1 medications at bedtime was also significantly associated with lower asleep systolic (SBP) and diastolic BP (DBP) means than treatment with all medications upon awakening. Sleep-time relative SBP and DBP decline was significantly attenuated in patients ingesting all medications upon awakening (p < .001). Thus, the prevalence of non-dipping was significantly higher when all hypertension medications were ingested upon awakening (68.6%) than when ≥1 of them was ingested at bedtime (55.8%; p < .001 between groups), and even further attenuated (49.7%) when all of them were ingested at bedtime (p < .001). Additionally, prevalence of the riser BP pattern, associated with highest CVD risk, was much greater (23.6%) among patients ingesting all medications upon awakening, compared with those ingesting some (20.0%) or all medications at bedtime (12.2%; p < .001 between groups). The latter group also showed significantly higher prevalence of properly controlled ambulatory BP (p < .001) that was achieved by a significantly lower number of hypertension medications (p < .001) compared with patients treated upon awakening. Our findings demonstrate significantly lower asleep SBP mean and attenuated prevalence of a blunted nighttime BP decline, i.e., lower prevalence of markers of CVD risk, and improved metabolic profile in patients with type 2 diabetes ingesting hypertension medications at bedtime than in those ingesting all of them upon awakening. These collective findings indicate that bedtime hypertension treatment, in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of hypertension and avoid treatment-induced nocturnal hypotension, should be the preferred therapeutic scheme for type 2 diabetes. (Author correspondence: rhermida@uvigo.es)