Sleep-time Systolic Blood Pressure Research Articles

Diabetes mellitus is associated with high sleep-time systolic blood pressure and non-dipping pattern

ABSTRACT Introduction Compared to clinic blood pressure (BP), sleep-time BP and non-dipping BP pattern are better predictors of target organ damage and cardiovascular sequalae. Aim In a retrospective study, we determined whether diabetes mellitus (DM) status is associated with high sleep-time BP and non-dipping pattern. Methods We analyzed 1092 patients who underwent ambulatory BP monitoring between 2015 and 2017 in a tertiary cardiology institution. During a 24-hour period, BP was automatically measured every 15 minutes between 7:00 AM and 11:59 PM and every 30 minutes thereafter. Results Compared with the non-DM group (n = 910), the DM group (n = 182) had a higher 24-hour systolic BP (137 ± 17 vs. non-DM, 132 ± 14 mmHg, p < 0.001) and sleep-time systolic BP (132 ± 20 vs. 123 ± 16 mmHg, p < 0.001), and was more likely to exhibit non-dipping (63% vs 42%, p˂0.001). The DM group was also less likely to meet the guideline-recommended target of 120/70 mmHg for the sleep-time BP measured via ambulatory monitoring (22% vs. 34%, p = 0.002). After adjusting for the effects of age, sex, body mass index, smoking, urea, eGFR, previous myocardial infarction, previous percutaneous coronary intervention, previous coronary artery bypass surgery, and previous stroke, DM remained a significant independent predictor of a higher 24-hour systolic BP (coefficient: 2.8, 95% confidence interval: 0.1–5.5, p = 0.042) and higher sleep-time systolic BP (coefficient: 4.2, 95% confidence interval: 1.1–7.3, p = 0.008). There was a trend toward more sleep-time non-dipping BP pattern (odds ratio: 1.4, 95% confidence interval: 1.0–2.0, p = 0.087) in the DM group. Conclusion DM is independently associated with suboptimal 24-hour BP control. This association is mainly attributed to a high sleep-time systolic BP.

Absence Of Sympathetic Vasodilation During Mental Stress With Non‐Dipping Circadian Blood Pressure Pattern In Young White And Black Adults Could Be An Early Indicator Of Hypertension

People of Black African ethnicity (BA) have greater prevalence of hypertension compared with those of White European ethnicity (WE) and are at greater risk of developing hypertension‐associated cardiovascular disease (CVD). Older WE non‐dipper hypertensives show endothelial dysfunction. Endothelial dysfunction and higher prevalence of non‐dipping nocturnal blood pressure have been documented in Blacks relative to Whites. Novel environmental stress stimuli evoke sympathetic vasoconstriction in renal and splanchnic vasculature, but vasodilatation in limb muscle, which may habituate on repetition. In young adults altered response to novel stimuli is predictive of developing hypertension later on in life. However, It is not known whether non‐dippers also show endothelial dysfunction and altered responses to environmental stressors. Thus, we hypothesized that non dippers would show smaller muscle vasodilator or muscle vasoconstrictive responses on repetition of an environmental stressor and blunted reactive hyperaemia relative to dippers. Experiments were performed on 17 WEs (21±0.64 years) and 16 BAs (22±0.77 years) who were resident in the UK. Responses were recorded following release of arterial occlusion for 2 min (reactive hyperaemia) and by 5 sound stimuli (S1–5; 100 dB, 2 KHz). Continuous arterial blood pressure (ABP) was recorded by finger photoplethysmography. Forearm blood flow (FBF) was recorded by venous occlusion plethysmography; forearm vascular conductance (FVC) was calculated as FBF/ABP. 24 hour Ambulatory blood pressure monitoring was done. Relative to WES, BAs showed higher 24 hour systolic blood pressure (SBP)(110±1.33 vs 117±3.17 mmHg) and higher sleep‐time SBP (99±1.36 vs 108±3.05 mmHg) p&lt;0.05 as well as higher proportion of pre‐/hypertensives (7/16, 40%) compared with WE (1,5.8%). 40% BAs were non‐ dippers compared to 17.6 % WE. Six of the pre‐/hypertensive BAs were nocturnal dippers. Relative to normotensive BA dippers, BA non‐dippers showed higher sleep SBP (93±4.65 vs 108±3.01 mmHg) and heart rate (59±4.69 vs 72±3.11 bpm) p&lt;0.05. Relative to WE dippers, the WE non dippers showed higher day‐time and night time mean ABP (85.25±1.14 vs 91.57±2.39 mmHg) ; (71.55±0.88 vs 81.25±1.71 mmHg) p&lt;0.05. During reactive hyperaemia, there was no difference between dippers and non‐dippers in the two ethnic groups ( WE: +0.39± 0.03 vs +0.45± 0.08; BA : +0.41± 0.05 vs +0.34± 0.05 p&gt;0.05 ). During S1–5, WE and BA dippers showed a net increase in FVC indicating forearm vasodilatation (WE, +0.005±0.002 CU; BA, +0.007±0.002 CU) whilst WE and BA non‐dippers showed a net decrease in FVC indicating forearm vasoconstriction, (WE − 0.007±0.004 CU; BA −0.007±0.003 CU). These results indicate that in young normotensive non‐dippers, sympathetic vasoconstriction to mental stress precedes development of endothelial dysfunction and could serve as an early indicator of cardiovascular disorder. Thus, we propose that exaggerated sympathetic vasoconstrictor response to environmental stressors contributes to the development of hypertension and CVD in non‐dippersThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

PP.34.03

Objective: Several features of ambulatory (ABPM) blood pressure (BP) have been explored as potential predictors of stroke. Some studies, limited among other factors by relying on a single, low reproducible 24 h ABPM per participant, use of arbitrarily fixed clock hours to defined awake and asleep spans, and/or analysis of the prognostic value of a single unadjusted ABPM-derived parameter, have concluded that elevated morning BP surge or increased BP variability might be significant markers of stroke. We evaluated the comparative prognostic value for stroke of clinic BP and multiple ABPM-derived characteristics among the participants in the Hygia Project, designed to evaluate prospectively CVD risk by ABPM in primary care centers of Northwest Spain. Design and method: This study involved 11255 subjects, 6028 men/5227 women, 58.9 ± 14.5 years of age, with baseline BP ranging from normotension to hypertension according to ABPM criteria, prospectively evaluated throughout a 4.0-year median follow-up. BP was measured at 20-min intervals from 07:00 to 23:00 h and every 30-min at night for 48 h. During monitoring, subjects maintained a diary listing the times of going to bed and awakening. Results: We documented 147 ischemic and 29 hemorrhagic strokes. When each ABPM-derived parameter was analyzed separately, the asleep systolic BP mean was the most significant predictor of stroke (adjusted hazard ratio 1.35; 95%CI [1.20–1.52] for each 1-SD increase; P < 0.001). A greater morning BP surge was significantly associated with lower, not higher, stroke risk (0.87 [0.76–0.99], P = 0.042). After adjustment by asleep BP, neither clinic BP nor any other ABPM-derived parameter, including awake and 48 h means, sleep-time relative BP decline, morning surge, and indices of awake, asleep and 24 h BP variability, was significantly associated with increased/decreased risk of stroke. Conclusions: Progressively elevated sleep-time systolic BP was the only significant and independent prognostic marker of stroke. Contrary to current believe, neither a greater morning BP surge, morning hypertension, or extreme-dipper BP patterning increased the risk of stroke after adjusting by asleep BP level. On the basis of the null prognostic value of clinic BP here corroborated, ABPM should be considered a clinical requirement for proper stroke risk stratification.

PP.35.29

Objective: In hypertension, ingesting blood pressure (BP)-lowering medications at bedtime, compared to ingesting them upon awakening, is associated with significant improved reduction of sleep-time BP mean, a sensitive prognostic marker of cardiovascular disease (CVD) risk, also identified as a predictor of the risk of developing chronic kidney disease (CKD). This randomized trial investigated if bedtime therapy with the entire daily dose of at least one hypertension medication exerts greater reduction in the risk for developing CKD than morning-time therapy with all medications. Design and method: We conducted a prospective, randomized, open-label, blinded endpoint trial on 2078 hypertensive patients without CKD, 1017 men/1061 women, 53.6 ± 13.7 years of age. Patients were randomized to ingest all their prescribed hypertension medications upon awakening or the entire daily dose of at least one 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 48 h to accurately derive the awake and asleep BP means. Results: 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). Participants ingesting at least one 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). Conclusions: 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.

PP.05.07

Objective: Recent guidelines suggest relying on the ambulatory blood pressure (BP) monitoring (ABPM) derived awake mean to corroborate the diagnosis of hypertension suspected by elevated clinic BP measurement. However, several prospective ABPM studies have found elevated sleep-time BP is a better predictor of cardiovascular disease (CVD) risk than awake BP mean, also in diabetes. We evaluated the combined contribution to CVD risk of clinic, awake, and asleep BP among patients with diabetes participants in the Hygia Project, designed to evaluate prospectively CVD risk by ABPM in primary care centers of Northwest Spain. Design and method: This study involved 2632 patients with type 2 diabetes, 1589 men/1043 women, 65.1 ± 11.6 years of age, with baseline BP ranging from normotension to sustained hypertension according to ABPM criteria, prospectively evaluated throughout a 4.1-year median follow-up. BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h. During monitoring, subjects maintained a diary listing the times of going to bed at night and awakening in the morning. Results: The hazard ratios (HR) of total CVD events for each 1-SD elevation in clinic, awake, and asleep systolic BP (SBP) analyzed separately (adjusted for the significant influential characteristics of age, sex, chronic kidney disease, cigarette smoking, waist perimeter, and history of previous CVD event) were 1.25 [95%CI: 1.17–1.35]; 1.39 [1.30–1.50], and 1.51 [1.41–1.62], respectively (always P < 0.001). Exploration of the combined contribution of all three BP measurements revealed elevation in asleep SBP (HR = 1.55 [1.38–1.75], P < 0.001) but not in clinic BP (1.08 [0.99–1.18], P = 0.082) or awake BP (0.93 [0.82–1.06], P = 0.270) was the only independent BP parameter significantly associated with increased CVD risk. Conclusions: In patients with diabetes, sleep-time SBP mean, but not daytime clinic BP measurement or ABPM-derived awake BP mean, is the only significant and independent prognostic marker of CVD morbidity and mortality. These findings indicate ABPM, but not conventional clinic BP so far mistakenly used to diagnose hypertension and establish therapeutic targets, is a clinical necessity to accurately detect abnormal sleep-time BP and assess CVD risk in diabetes.

Sleep-time blood pressure as a therapeutic target for reducing the risk of developing diabetes

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 diabetes (DM). Additionally, asleep BP has been identified as an independent prognostic marker for new-onset DM. However, the potential reduction in the risk of DM associated with decreasing an elevated asleep BP mean has never before been investigated. We prospectively evaluated whether reduced risk of new-onset DM is more related to the progressive decrease of clinic, awake, or asleep BP. We investigated 2656 subjects without DM, 1292 men/1364 women, 50.6 14.3 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 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. During a 5.6-year median follow-up, 190 participants developed DM. Using baseline data, when asleep BP was adjusted by awake BP mean, only the former was a significant predictor of new-onset DM in a Cox proportional-hazard model adjusted for age, waist perimeter, glucose, and chronic kidney disease. Analyses of changes in BP during follow-up revealed a 30% reduction in the risk of developing DM 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 during follow-up. Only the increase in sleep-time relative SBP mean towards more normal dipper patterning improved the prognostic value of sleep-time SBP (adjusted hazard ratio 0.82 [95%CI: 0.70-0.96], P1⁄40.013). Sleep-time SBP mean is the most significant independent prognostic marker of new-onset DM. 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, were the most significant independent predictors of reduced risk of developing DM.

The relationship between metabolic parameters and quality of life in the patients with type 2 diabetes mellitus concomitant hypertension

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 diabetes (DM). Additionally, asleep BP has been identified as an independent prognostic marker for new-onset DM. However, the potential reduction in the risk of DM associated with decreasing an elevated asleep BP mean has never before been investigated. We prospectively evaluated whether reduced risk of new-onset DM is more related to the progressive decrease of clinic, awake, or asleep BP. We investigated 2656 subjects without DM, 1292 men/1364 women, 50.6 14.3 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 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. During a 5.6-year median follow-up, 190 participants developed DM. Using baseline data, when asleep BP was adjusted by awake BP mean, only the former was a significant predictor of new-onset DM in a Cox proportional-hazard model adjusted for age, waist perimeter, glucose, and chronic kidney disease. Analyses of changes in BP during follow-up revealed a 30% reduction in the risk of developing DM 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 during follow-up. Only the increase in sleep-time relative SBP mean towards more normal dipper patterning improved the prognostic value of sleep-time SBP (adjusted hazard ratio 0.82 [95%CI: 0.70-0.96], P1⁄40.013). Sleep-time SBP mean is the most significant independent prognostic marker of new-onset DM. 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, were the most significant independent predictors of reduced risk of developing DM.

Effects of Azilsartan Compared to Other Angiotensin Receptor Blockers on Left Ventricular Hypertrophy and the Sympathetic Nervous System in Hemodialysis Patients

Hypertension is a major risk factor for cardiovascular and cerebrovascular events, and most patients with hypertension are administered antihypertensive drugs. However, not all patients achieve normal blood pressure levels. The new angiotensin receptor blocker azilsartan (Takeda Pharmaceutical Company Limited, Osaka, Japan) has been reported to have a strong hypotensive effect. Our study investigated the efficacy of azilsartan compared with other angiotensin receptor blockers. This study included 17 hypertensive patients on HD, who had been administered angiotensin receptor blockers, except for azilsartan, for more than 6 months before enrolling, and after enrollment, they were switched to azilsartan. Blood tests, Holter electrocardiogram, ambulatory blood pressure monitoring, and echocardiography were performed at baseline and at the 6-month follow-up. The blood pressure from baseline to 6 months had significantly decreased (24-h systolic blood pressure from 150.9 ± 16.2 mm Hg to 131.3 ± 21.7 mm Hg, P = 0.008), awakening time systolic blood pressure from 152.1 ± 16.9 mm Hg to 131.7 ± 23.2 mm Hg, P = 0.01, sleep-time systolic blood pressure from 148.1 ± 19.7 mm Hg to 130.0 ± 20.1 mm Hg, P = 0.005). There was a significant reduction in serum noradrenaline levels as well as left ventricular mass index after switching to azilsartan (from 550.1 ± 282.9 pg/mL, to 351.7 ± 152.3 pg/mL, P = 0.002; from 117.0 ± 26.4 g/m(2) to 111.3 ± 23.9 g/m(2), P = 0.01, respectively). Azilsartan had a significantly stronger hypotensive effect than other angiotensin receptor blockers. Thus, the switch to azilsartan might improve prognosis of hemodialysis patients. We suggest that the strong anti-hypertensive effect of azilsartan originated from a combination of primary angiotensin receptor blocker class-effect and a stronger suppression of sympathetic nervous system.

Cardiovascular Risk of Resistant Hypertension: Dependence on Treatment-Time Regimen of Blood Pressure–Lowering Medications

In resistant hypertension, ingesting one or more blood pressure (BP)-lowering medications at bedtime is associated with significant reduction of sleep-time BP, a sensitive prognostic marker of cardiovascular disease (CVD) risk. This randomized trial investigated if bedtime therapy with at least one hypertension medication exerts better BP control and CVD risk reduction than conventional, morning-time therapy with all medications. We conducted a prospective, open-label, blinded-endpoint trial on 776 patients (387 men/389 women) with resistant hypertension, 61.6 ± 11.2 (mean ± SD) yrs of age. Patients were randomized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime. BP was measured by ambulatory monitoring for 48 h at baseline, and again annually or more frequently (quarterly) if treatment adjustment was required. After a median follow-up of 5.4 yrs (range, .5–8.5 yrs), participants ingesting ≥1 hypertension medications at bedtime showed a significantly lower hazard ratio (HR) of total CVD events (adjusted by age, sex, and diabetes) than those ingesting all medications upon awakening (.38 [95% CI: .27–.55]; number of events 102 vs. 41; p < .001). The difference between groups in the adjusted HR of major CVD events (a composite of CVD death, myocardial infarction, ischemic stroke, and hemorrhagic stroke) was also statistically significant (.35 [95% CI: .18–.68]; number of events 32 vs. 12; p = .002). At the last evaluation, patients treated with the bedtime versus awakening-time-treatment regimen showed significantly lower sleep-time systolic/diastolic BP mean values (121.6/65.4 vs. 113.0/61.1 mm Hg; p < .001) and higher prevalence of controlled ambulatory BP (61% vs. 46%; p < .001). The progressive decrease in the sleep-time systolic BP mean during follow-up was the most significant predictor of event-free survival (15% risk reduction per 5 mm Hg decreased asleep systolic BP mean). Among patients with resistant hypertension, ingestion of at least one hypertension medication at bedtime, compared with all medications upon waking, resulted in improved ambulatory BP control and fewer hard and soft CVD events. (Author correspondence: rhermida@uvigo.es)

Effects of occupational noise exposure on blood pressure.

We measured 24-hour ambulatory blood pressure and 16-hour noise exposure continuously for 20 automobile workers, and used linear mixed-effects regression models to estimate transient and sustained effects of noise exposure on blood pressure. The occupational noise levels of the high-exposure workers with 85 +/- 8 dBA were significantly higher than those of the low-exposure workers with 59 +/- 4 dBA (P < 0.05). We found a significant difference of 16 +/- 6 mm Hg in sleep-time systolic blood pressure (SBP) existed between 2 exposure groups, and a marginal increase of 1 mm Hg SBP per 1-dBA increase in occupational noise exposure at a 60-minute lag time during work (P = 0.07). Occupational noise exposure had both transient and sustained effects on workers' SBP.