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

Abstract

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 signific...

Bedtime ingestion of hypertension medications reduces the risk of new-onset type 2 diabetes: a randomised controlled trial

“…Finally, antagonism of the RAAS by reduction of angiotensin II formation and blockade of its receptors achieved either by a bedtime ACEI or ARB ingestion strategy is superior to any other treatment strategy for reducing risk of new-onset diabetes. Future prospective intervention trials that incorporate periodic, annually or more frequent, ABPM assessments during long-term follow-up evaluation, as done in the MAPEC study and the currently ongoing multicentre Hygia project [38,39], are necessary to confirm the reduced risk of new-onset diabetes by bedtime hypertension chronotherapy.…”

Hipertensión Arterial Y Diabetes: Guías De Recomendaciones Para La Práctica Clínica. 2015. Comité De Hipertensión Arterial Y Otros FRCV- Sad

“…El impacto de la administración nocturna sobre la regulación de la PA parece tener un efecto clínico importante, ya que mediante el MAPA se mostró una asociación entre el patrón non-dipper nocturno y un incremento en la incidencia de eventos CV fatales y no fatales; este patrón non-dipper y la HA nocturna es altamente predominante en pacientes con DM2 128 .…”

Effects of Morning versus Evening Administration of Perindopril on the Circadian Control of Blood Pressure in Cameroonian Type 2 Diabetes Individuals: A Crossover Randomized Trial

“…Clinical practice guidelines are unanimous on the pivotal role of angiotensinconverting enzyme inhibitors (ACEIs) and angiotensin receptors antagonists in BP lowering strategies in people with diabetes [12]. It has been suggested that compared to morning ingestion, bedtime ingestion of more than one antihypertensive drug could induce a better reduction of incident cardiovascular events in type 2 diabetes patients [13]. Perindopril is a long acting ACEI, which displays similar pharmacodynamic properties to other agents in this class.…”