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Sleep-time blood pressure as a therapeutic target for reducing the risk of developing chronic kidney disease
Abstracts / Journal of the American Society of Hypertension 9(4S) (2015) e75–e83 53.613.7 years of age. Patients were randomized to ingest all their prescribed hypertension medications upon awakening or the entire daily dose of 1 of them at bedtime. At baseline and annually (or more frequently if hypertension treatment was adjusted based on ambulatory BP) thereafter, BP and physical activity (wrist actigraphy) were simultaneously monitored for 48h to accurately derive the awake and asleep BP means. During a 5.9-year median follow-up, 368 patients developed CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2, albuminuria, or both, at least twice within 3 months). The Kaplan-Meier survival curves indicated a highly significant difference between treatment-time groups in event-free survival (log-rank 119.7, P<0.001). Participants ingesting 1 BP-lowering medications at bedtime showed a significantly lower hazard ratio (HR) of new-onset CKD (adjusted by the significant influential characteristics of age, waist perimeter, diabetes, sleep-time systolic BP mean, and sleep-time relative systolic BP decline) than those ingesting all medications upon awakening (0.28 [95%CI: 0.22-0.36]; event-rate 8.3 vs. 27.1%; P<0.001). There was an even further benefit in preventing CKD among patients ingesting not just one but all BP-lowering medications at bedtime (event-rate 3.8 vs. 13.5% in patients ingesting medications both upon awakening and at bedtime; P<0.001). In hypertensive patients without CKD, ingestion of at least one, preferably all, BP-lowering medication at bedtime, compared to ingestion of all medications upon-awakening, resulted in improved ambulatory BP control (significant further reduction of asleep BP and enhanced sleep-time relative BP decline) and markedly reduced prevalence of new-onset CKD. Keywords: Chronic kidney disease; chronotherapy; antihypertensive treatment
P-135 Prognostic impact of sleep-time relative blood pressure decline for predicting the risk of developing chronic kidney disease Ramon C. Hermida, Diana E. Ayala, Maria J. Fontao, Artemio Mojon, Jose R. Fernandez. University of Vigo, Vigo, Spain Numerous studies have consistently shown an association between elevated sleep-time blood pressure (BP) and non-dipping with increased incidence of fatal and non-fatal cardiovascular events, although the relationship between the extreme-dipper BP pattern and risk remains controversial. Sleep-time hypertension and non-dipping are highly prevalent in chronic kidney disease (CKD), although the potential prognostic value of these BP alterations for the development of CKD has not been properly investigated. We evaluated the prognostic impact for the risk of CKD of both the sleep-time-relative BP decline as a continuous variable and dipping classification as a categorical one. We prospectively evaluated 2763 subjects without CKD, 1343 men/1420 women, 51.514.3 years of age, with baseline ambulatory BP (ABPM) ranging from normotension to sustained hypertension. At baseline and annually (or more frequently if hypertension treatment was adjusted based on ABPM) thereafter, ambulatory BP and physical activity (wrist actigraphy) were simultaneously monitored for 48h to accurately derive the awake and asleep BP means. The Cox proportional-hazard model, adjusted for significant confounding variables, was used to estimate hazard ratios (HR) for the risk of developing CKD associated with sleep-time-relative BP decline and dipping classification. During a 5.9-year median follow-up, 404 participants developed CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2, albuminuria, or both, at least twice within 3 months). A diminished sleep-time relative BP decline was a highly significant predictor of CKD in a Cox proportional-hazard model adjusted for the significant influential variables of age, waist perimeter, diabetes, duration of sleep, and previous CVD event (for each 1-SD elevation, HR¼0.70, [95%CI: 0.64-0.76], P<0.001). Based on either the baseline or the last available 48h ABPM evaluation per participant, the adjusted HR was lowest in extreme-dippers (P¼0.061) and significantly higher in non-dippers and risers (P<0.001) compared with normal dipper BP patterning. The risk of developing CKD decreased in
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extreme-dippers during follow-up, during which sleep-time hypotension was avoided by proper use of ABPM-based timed pharmacotherapy. The HR of new-onset CKD was significantly greater in non-dippers and, to a larger extent in risers. Results indicate a blunted sleep-time relative BP decline predicts the development of CKD, rather than being a consequence of this condition. Keywords: Chronic kidney disease; asleep blood pressure; ambulatory blood pressure monitoring
P-136 Sleep-time blood pressure as a therapeutic target for reducing the risk of developing chronic kidney disease Ramon C. Hermida, Diana E. Ayala, Maria J. Fontao, Artemio Mojon, Jose R. Fernandez. University of Vigo, Vigo, Spain Independent studies have found that elevated sleep-time blood pressure (BP) is a better predictor of cardiovascular disease (CVD) risk than the awake or 24h BP means in patients without as well as with chronic kidney disease (CKD). Additionally, asleep BP has been identified as an independent prognostic marker for the development of CKD. However, the potential reduction in the risk of CKD associated with decreasing the asleep BP mean has never before been investigated. We prospectively evaluated whether reduced risk of CKD is more related to the progressive treatment-induced decrease of clinic, awake, or asleep BP. We evaluated 2763 subjects without CKD, 1343 men/1420 women, 51.514.3 years of age, with baseline ambulatory BP ranging from normotension to sustained hypertension. At baseline and annually (or more frequently if hypertension treatment was adjusted) thereafter, ambulatory BP and physical activity (wrist actigraphy) were simultaneously monitored for 48h to accurately derive the awake and asleep BP means. During a 5.9-year median follow-up, 404 participants developed CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2, albuminuria, or both, at least twice within 3 months). Analyses of changes in clinic and ambulatory BP during follow-up revealed a 27% reduction in the risk of developing CKD for each 1-SD decrease in asleep systolic BP (SBP) mean (P<0.001), independent of changes in daytime clinic or ABPM-derived awake BP mean, neither associated to decreased risk. Only the progressive increase in sleep-time relative SBP mean towards more normal dipper BP patterning during follow-up improved the prognostic value of sleep-time SBP (adjusted hazard ratio 0.81 [95%CI: 0.73-0.90], P<0.001). The sleeptime SBP mean derived from ambulatory BP monitoring (ABPM) is the most significant independent prognostic marker of new-onset CKD. More important, decreasing asleep SBP and increasing sleep-time relative SBP decline, two novel therapeutic targets requiring proper patient evaluation by ABPM and more feasible by bedtime than morning hypertension treatment, are the most significant independent predictors of reduced risk of developing CKD. Keywords: Chronic kidney disease; asleep blood pressure; ambulatory blood pressure monitoring
P-137 Influence of class and treatment-time regimen of hypertension medications on the risk of developing chronic kidney disease Ramon C. Hermida, Diana E. Ayala, Artemio Mojon, Jose R. Fernandez. University of Vigo, Vigo, Spain Many prospective trials have documented the safety and effects on the 24h blood pressure (BP) pattern of several classes of hypertension medications are greatly improved when ingested at bedtime rather than upon awakening. For example, bedtime versus morning ingestion of ACEIs and ARBs better controls the asleep BP mean, thus converting the 24h BP profile into more normal dipper patterning. Recent findings further indicate
P-135 Prognostic impact of sleep-time relative blood pressure decline for predicting the risk of developing chronic kidney disease Ramon C. Hermida, Diana E. Ayala, Maria J. Fontao, Artemio Mojon, Jose R. Fernandez. University of Vigo, Vigo, Spain Numerous studies have consistently shown an association between elevated sleep-time blood pressure (BP) and non-dipping with increased incidence of fatal and non-fatal cardiovascular events, although the relationship between the extreme-dipper BP pattern and risk remains controversial. Sleep-time hypertension and non-dipping are highly prevalent in chronic kidney disease (CKD), although the potential prognostic value of these BP alterations for the development of CKD has not been properly investigated. We evaluated the prognostic impact for the risk of CKD of both the sleep-time-relative BP decline as a continuous variable and dipping classification as a categorical one. We prospectively evaluated 2763 subjects without CKD, 1343 men/1420 women, 51.514.3 years of age, with baseline ambulatory BP (ABPM) ranging from normotension to sustained hypertension. At baseline and annually (or more frequently if hypertension treatment was adjusted based on ABPM) thereafter, ambulatory BP and physical activity (wrist actigraphy) were simultaneously monitored for 48h to accurately derive the awake and asleep BP means. The Cox proportional-hazard model, adjusted for significant confounding variables, was used to estimate hazard ratios (HR) for the risk of developing CKD associated with sleep-time-relative BP decline and dipping classification. During a 5.9-year median follow-up, 404 participants developed CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2, albuminuria, or both, at least twice within 3 months). A diminished sleep-time relative BP decline was a highly significant predictor of CKD in a Cox proportional-hazard model adjusted for the significant influential variables of age, waist perimeter, diabetes, duration of sleep, and previous CVD event (for each 1-SD elevation, HR¼0.70, [95%CI: 0.64-0.76], P<0.001). Based on either the baseline or the last available 48h ABPM evaluation per participant, the adjusted HR was lowest in extreme-dippers (P¼0.061) and significantly higher in non-dippers and risers (P<0.001) compared with normal dipper BP patterning. The risk of developing CKD decreased in
e79
extreme-dippers during follow-up, during which sleep-time hypotension was avoided by proper use of ABPM-based timed pharmacotherapy. The HR of new-onset CKD was significantly greater in non-dippers and, to a larger extent in risers. Results indicate a blunted sleep-time relative BP decline predicts the development of CKD, rather than being a consequence of this condition. Keywords: Chronic kidney disease; asleep blood pressure; ambulatory blood pressure monitoring
P-136 Sleep-time blood pressure as a therapeutic target for reducing the risk of developing chronic kidney disease Ramon C. Hermida, Diana E. Ayala, Maria J. Fontao, Artemio Mojon, Jose R. Fernandez. University of Vigo, Vigo, Spain Independent studies have found that elevated sleep-time blood pressure (BP) is a better predictor of cardiovascular disease (CVD) risk than the awake or 24h BP means in patients without as well as with chronic kidney disease (CKD). Additionally, asleep BP has been identified as an independent prognostic marker for the development of CKD. However, the potential reduction in the risk of CKD associated with decreasing the asleep BP mean has never before been investigated. We prospectively evaluated whether reduced risk of CKD is more related to the progressive treatment-induced decrease of clinic, awake, or asleep BP. We evaluated 2763 subjects without CKD, 1343 men/1420 women, 51.514.3 years of age, with baseline ambulatory BP ranging from normotension to sustained hypertension. At baseline and annually (or more frequently if hypertension treatment was adjusted) thereafter, ambulatory BP and physical activity (wrist actigraphy) were simultaneously monitored for 48h to accurately derive the awake and asleep BP means. During a 5.9-year median follow-up, 404 participants developed CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2, albuminuria, or both, at least twice within 3 months). Analyses of changes in clinic and ambulatory BP during follow-up revealed a 27% reduction in the risk of developing CKD for each 1-SD decrease in asleep systolic BP (SBP) mean (P<0.001), independent of changes in daytime clinic or ABPM-derived awake BP mean, neither associated to decreased risk. Only the progressive increase in sleep-time relative SBP mean towards more normal dipper BP patterning during follow-up improved the prognostic value of sleep-time SBP (adjusted hazard ratio 0.81 [95%CI: 0.73-0.90], P<0.001). The sleeptime SBP mean derived from ambulatory BP monitoring (ABPM) is the most significant independent prognostic marker of new-onset CKD. More important, decreasing asleep SBP and increasing sleep-time relative SBP decline, two novel therapeutic targets requiring proper patient evaluation by ABPM and more feasible by bedtime than morning hypertension treatment, are the most significant independent predictors of reduced risk of developing CKD. Keywords: Chronic kidney disease; asleep blood pressure; ambulatory blood pressure monitoring
P-137 Influence of class and treatment-time regimen of hypertension medications on the risk of developing chronic kidney disease Ramon C. Hermida, Diana E. Ayala, Artemio Mojon, Jose R. Fernandez. University of Vigo, Vigo, Spain Many prospective trials have documented the safety and effects on the 24h blood pressure (BP) pattern of several classes of hypertension medications are greatly improved when ingested at bedtime rather than upon awakening. For example, bedtime versus morning ingestion of ACEIs and ARBs better controls the asleep BP mean, thus converting the 24h BP profile into more normal dipper patterning. Recent findings further indicate