***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 
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    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 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 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 0.28 ; 95 % CI 0.13 to 0.61 ; P < 0.001 ) . Furthermore , patients on bedtime treatment had a significantly lower mean sleep-time BP and a greater proportion demonstrated control of their ambulatory BP ( 56 % versus 45 % , P = 0.003 ) . Each 5-mmHg decrease in mean sleep-time systolic BP was associated with a 14 % reduction in the risk for cardiovascular events during follow-up ( P < 0.001 ) . In conclusion , among patients with CKD and hypertension , taking at least one antihypertensive medication at bedtime improves control of BP and reduces the risk for cardiovascular events Previous results have indicated that valsartan administration at bedtime as opposed to on wakening improves the diurnal/nocturnal ratio of blood pressure without loss in efficacy and therapeutic coverage . We hypothesized that increasing this ratio could reduce microalbuminuria . We conducted a prospect i ve , r and omized , open-label , blinded endpoint trial on 200 previously untreated nonproteinuric patients with grade 1 to 2 essential hypertension , assigned to receive valsartan ( 160 mg/d ) as a monotherapy either on awakening or at bedtime .  Blood pressure was measured by ambulatory monitoring for 48 consecutive hours before and after 3 months of treatment . Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis . The significant blood pressure reduction after 3 months of therapy was similar for both treatment times . The diurnal/nocturnal blood pressure ratio was unchanged after valsartan on awakening , but significantly increased from 7.5 to 12.2 ( P<0.001 ) when valsartan was administered at bedtime . Urinary albumin excretion was significantly reduced by 41 % after bedtime treatment . This reduction was independent of the 24-hour blood pressure decrease but highly correlated with the decrease in nocturnal blood pressure and mainly with the increase in diurnal/nocturnal ratio ( P<0.001 ) . Bedtime valsartan administration improves the diurnal/nocturnal blood pressure ratio to a more dipper profile . This normalization of the circadian blood pressure pattern is associated with a significant decrease in urinary albumin excretion and plasma fibrinogen , and could thus reduce the increased cardiovascular risk in nondipper hypertensive patients The associations of  diastolic blood pressure ( DBP )  with  stroke  and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any " threshold " below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at " baseline " with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this " regression dilution " bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrect 
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No significant difference was noted in all-cause mortality and cardiovascular mortality .
Conclusion This meta- analysis suggests that chronotherapy could reduce nocturnal BP in hypertensive CKD patients