***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT The clinical use of ambulatory blood pressure ( BP ) monitoring requires further validation in prospect i ve outcome studies . OBJECTIVE To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension . DESIGN Sub study to the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) Trial , started in October 1988 with follow up to February 1999 . The conventional BP at r and omization was the mean of 6 readings ( 2 measurements in the sitting position at 3 visits 1 month apart ) . The baseline ambulatory BP was recorded with a noninvasive intermittent technique . SETTING Family practice s and outpatient clinics at primary and secondary referral hospitals . PARTICIPANTS A total of 808 older ( aged > or = 60 years ) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic . INTERVENTIONS For the overall study , patients were r and omized to nitrendipine ( n = 415 ; 10 - 40 mg/d ) with the possible addition of enalapril ( 5 - 20 mg/d ) and /or hydrochlorothiazide ( 12.5 - 25.0 mg/d ) or to matching placebos ( n = 393 ) . MAIN OUTCOME MEASURES Total and cardiovascular mortality , all cardiovascular end points , fatal and nonfatal stroke , and fatal and nonfatal cardiac end points . RESULTS After adjusting for sex , age , previous cardiovascular complications , smoking , and residence in western Europe , a 10-mm Hg higher conventional systolic BP at r and omization was not associated with a worse prognosis , whereas in the placebo group , a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate ( HR ) of most outcome measures ( eg , HR , 1.23 [ 95 % confidence interval [ CI ] , 1.00 - 1.50 ] for total mortality and 1.34 [ 95 % CI , 1.03 - 1.75 ] for cardiovascular mortality ) . In the placebo group , the nighttime systolic BP ( 12 AM-6 AM ) more accurately predicted end points than the daytime level . Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP ( 10 % increase in night-to-day ratio ; HR for all cardiovascular end points , 1.41 ; 95 % CI , 1.03 - 1.94 ) . At r and omization , the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg ( 95 % CI , 128 - 156 mm Hg ) , 145 mm Hg ( 95 % CI , 126 - 164 mm Hg ) or 132 mm Hg ( 95 % CI , 120 - 145 mm Hg ) , respectively . In the active treatment group , systolic BP at r and omization did not significantly predict cardiovascular risk , regardless of the technique of BP measurement . CONCLUSIONS In untreated older patients with isolated systolic hypertension , ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP The objective of our study was to determine the effects of 2 antihypertensive drug dose schedules ( PM dose and add-on dose ) on nocturnal blood pressure ( BP ) in comparison with usual therapy ( AM dose ) in blacks with hypertensive chronic kidney disease and controlled office BP . In a 3-period , crossover trial , former participants of the African American Study of Kidney Disease were assigned to receive the following 3 regimens , each lasting 6 weeks , presented in r and om order : AM dose ( once-daily antihypertensive medications taken in the morning ) , PM dose ( once-daily antihypertensives taken at bedtime ) , and add-on dose ( once-daily antihypertensives taken in the morning and an additional antihypertensive medication before bedtime [ diltiazem 60–120 mg , hydralazine 25 mg , or additional ramipril 5 mg ] ) .  Ambulatory BP monitoring  was performed at the end of each period . The primary outcome was nocturnal systolic BP .  Mean age of the study population ( n=147 ) was 65.4 years , 64 % were men , and mean estimated glomerular filtration rate was 44.9 mL/min per 1.73 m2 . At the end of each period , mean ( SE ) nocturnal systolic BP was 125.6 ( 1.2 ) mm Hg in the AM dose , 123.9 ( 1.2 ) mm Hg in the PM dose , and 123.5 ( 1.2 ) mm Hg in the add-on dose . None of the pairwise differences in nocturnal , 24-hour , and daytime systolic BP was statistically significant . Among blacks with hypertensive chronic kidney disease , neither PM ( bedtime ) dosing of once-daily antihypertensive nor the addition of drugs taken at bedtime significantly reduced nocturnal BP compared with morning dosing of antihypertensive medications Nondipping blood pressure ( BP ) pattern is a potential independent risk factor for chronic kidney disease ( CKD ) . Bedtime administration of valsartan is considered to normalize circadian rhythm and protect the kidneys and heart in CKD patients . However , more clinical trials are needed to confirm this benefit . Sixty patients with nondipping BP pattern and thirty patients with dipping BP pattern were enrolled in this study , and the patients with nondipping BP pattern were r and omly divided into two groups and treated with bedtime or awakening doses of valsartan ( 80 - 320 mg ) . Nondipping BP patients treated with bedtime doses of valsartan showed a greater reduction in 24-hour proteinuria and bedtime proteinuria , a greater delayed decline in estimated glomerular filtration rate , and more protection against myocardial hypertrophy ( P<.05 ) compared with patients with the nondipping BP pattern treated with the awakening dose ( P<.05 ) . This was similar to patients with dipping BP . No severe clinical complications were recorded in these patients . Valsartan with bedtime dosing in CKD patients with the nondipping BP pattern have better renal and cardiovascular protection . Antihypertensive " chronotherapy " may be useful in clinical practice for CKD patients Many published prospect i ve trials have reported clinical ly meaningful morning-evening , treatment-time differences in the blood pressure (BP)-lowering efficacy , duration of action , and safety of most classes of hypertension medications . Most important , it was recently documented that routine ingestion of the full daily dose of ≥1 hypertension medications at bedtime , compared with ingestion of all of them upon awakening , significantly reduces cardiovascular disease ( CVD ) events . Nocturnal hypertension and non-dipping ( < 10 % decline in the asleep relative to the awake BP mean ) , as determined by ambulatory BP monitoring ( ABPM ) , are frequent in chronic kidney disease ( CKD ) and both are associated with increased CVD risk . Here , we investigated the influence of hypertension treatment time on the circadian BP pattern and degree of BP control of hypertensive patients with CKD evaluated by 48-h ABPM . This cross-sectional study evaluated 2659 such patients ( 1585 men/1074 women ) , 64.9 ± 13.2 ( mean ± SD ) yrs of age , enrolled in the Hygia Project , involving primary care centers of northwest Spain and design ed to evaluate prospect ively CVD risk by ABPM ; 1446 were ingesting all BP-lowering medications upon awakening , whereas 1213 patients were ingesting ≥1 medications at bedtime . Among the latter , 359 patients were ingesting all medications at bedtime , whereas 854 were ingesting the full daily dose of some medications upon awakening and the others at bedtime . Those ingesting all medications upon awakening had significantly higher total cholesterol and low-density lipoprotein ( LDL ) cholesterol than those ingesting ≥1 medications at bedtime . Moreover , patients ingesting all medications at bedtime had the lowest fasting glucose , serum creatinine , and uric acid . Ingestion of ≥1 medications at bedtime was significantly associated with lower asleep systolic ( SBP ) and diastolic ( DBP ) BP means than treatment with all medications upon awakening . The sleep-time relative SBP 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 ( 68.3 % ) than when ≥1 of them was ingested at bedtime ( 54.2 % ; p < .001 between groups ) , and even further attenuated ( 47.9 % ) when all of them were ingested at bedtime ( p < .001 ) . Additionally , the prevalence of a riser BP pattern , associated with highest CVD risk , was much greater ( 21.5 % ) among patients ingesting all medications upon awakening , compared with those ingesting some ( 15.7 % ) or all medications at bedtime ( 10.6 % ; p < .001 between groups ) , independent of CKD severity ( disease stage ) . The latter group also showed a 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 and DBP means and attenuated prevalence of a blunted nighttime BP decline , i.e. , lower prevalence of markers of CVD risk , in patients with CKD 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 CKD . ( Author correspondence : rhermida@uvigo.es The purpose of this study was to determine if ambulatory blood pressure measurement predicted total and cardiovascular mortality over and beyond clinic blood pressure measurement and other cardiovascular risk factors ; 5292 untreated hypertensive patients referred to a single blood pressure clinic who had clinic and ambulatory blood pressure measurement at baseline were followed up in a prospect i ve study of mortality outcome . Multiple Cox regression was used to model time to total and cause-specific mortality for ambulatory blood pressure measurement while adjusting for clinic blood pressure measurement and other risk factors at baseline . There were 646 deaths ( of which 389 were cardiovascular ) during a median follow-up period of 8.4 years . With adjustment for gender , age , risk indices , and clinic blood pressure , higher mean values of ambulatory blood pressure were independent predictors for cardiovascular mortality . The relative hazard ratio for each 10-mm Hg increase in systolic blood pressure was 1.12 ( 1.06 to 1.18 ; P<0.001 ) for daytime and 1.21 ( 1.15 to 1.27 ; P<0.001 ) for nighttime systolic blood pressure . The hazard ratios for each 5-mm Hg increase in diastolic blood pressure were 1.02 ( 0.99 to 1.07 ; P = NS ) for daytime and 1.09 ( 1.04 to 1.13 ; P<0.01 ) for nighttime diastolic pressures . The hazard ratios for nighttime ambulatory blood pressure remained significant after adjustment for daytime ambulatory blood pressure . These results have 2 important clinical messages : ambulatory measurement of blood pressure is superior to clinic measurement in predicting cardiovascular mortality , and nighttime blood pressure is the most potent predictor of outcome Time of ingestion of hypertension medications can affect circadian patterns of BP , but whether this translates into an effect on clinical outcomes is unknown . Here , in an open-label trial , we r and omly assigned 661 patients with CKD either to take all prescribed hypertension medications upon awakening or to take at least one of them at bedtime . We measured 48-hour ambulatory BP at baseline and 3 months after any adjustment in treatment or , at the least , annually . After a median follow-up of 5.4 years , patients who took at least one BP-lowering medication at bedtime had an adjusted risk for total cardiovascular events ( a composite of death , myocardial infa rct ion , angina pectoris , revascularization , heart failure , arterial occlusion of lower extremities , occlusion of the retinal artery , and stroke ) that was approximately one-third that of patients who took all medications upon awakening ( adjusted HR 0.31 ; 95 % CI 0.21 to 0.46 ; P < 0.001 ) . Bedtime dosing demonstrated a similar significant reduction in risk for a composite outcome of cardiovascular death , myocardial infa rct ion , and stroke ( adjusted HR 0. 
    Output:
    
Patients showed no significant differences for all-cause mortality and cardiovascular mortality .
CONCLUSION This review shows that evening dosing regimen drug therapy could reverse non-dipper BP patterns in hypertensive CKD patients