Sleep-time Blood Pressure Research Articles

Does Patient-Applied Testosterone Replacement Therapy Pose Risk for Blood Pressure Elevation? Circadian Medicine Perspectives.

We reviewed medication package inserts, US Food and Drug Administration (FDA) reports, and journal publications concerning the 10 nonbiosimilar patient-applied (PA) testosterone (T) replacement therapies (TRTs) for intraday serum T patterning and blood pressure (BP) effects. Blood T concentration is circadian rhythmic in young adult eugonadal males, being highest around awakening and lowest before bedtime. T level and 24 h variation are blunted in primary and secondary hypogonadism. Utilized as recommended, most PA-TRTs achieve nonphysiologic T 24 h patterning. Only Androderm® , an evening PA transdermal patch, closely replicates the normal T circadian rhythmicity. Accurate determination of risk for BP elevation and hypertension (HTN) by PA-TRTs is difficult due to limitations of office BP measurements (OBPM) and suboptimal methods and endpoints of ambulatory BP monitoring (ABPM). OBPM is subject to "White Coat" pressor effect resulting in unrepresentative BP values plus masked normotension and masked HTN, causing misclassification of approximately 45% of trial participants, both before and during treatment. Change in guideline-recommended diagnostic thresholds over time causes misclassification of an additional approximately 15% of participants. ABPM is improperly incorporated into TRT safety trials. It is done for 24 h rather than preferred 48 h; BP is oversampled during wakefulness, biasing derived 24 h mean values; 24 h mean systolic and diastolic BP (SBP, DBP) are inappropriate primary outcomes, because of not being best predictors of risk for major acute cardiovascular events (MACE); "daytime" and "nighttime" BP means referenced to clock time are reported rather than biologically relevant wake-time and sleep-time BP means; most importantly, asleep SBP mean and dipping, strongest predictors of MACE, are disregarded. © 2022 American Physiological Society. Compr Physiol 12: 1-20, 2022.

Effects of Experimental Sleep Restriction on Ambulatory and Sleep Blood Pressure in Healthy Young Adults: A Randomized Crossover Study.

[Figure: see text].

Chronotherapy of Hypertension with Angiotensin Receptor Blockers–A Meta-Analysis of Blood Pressure Measured by Ambulatory Blood Pressure Monitoring in Randomized Trials

BackgroundWe performed this meta-analysis evaluating the efficacy of chronotherapy of hypertension with angiotensin receptor blockers (ARBs). MethodsWe searched Pubmed, Web of Science, and Cochrane for all published randomized trials that compare antihypertensive effects of ARBs between bedtime dosing and awakening dosing. Blood pressure (BP) was measured by ambulatory BP monitoring in patients with mild or moderate essential hypertension. ResultsThe effects of ARBs on BP were assessed in 805 essential hypertensive patients included in 8 trials with a follow-up of 12 ± 3 weeks. The sleep-time systolic and diastolic BP (SBP, DBP) with bedtime dosing greatly decreased as compared with awakening dosing (weighted mean differences [WMD] for SBP WMD −5.23 [95% confidence intervals (CI), −7.27, −3.20] mm Hg, p < 0.001; WMD for DBP −2.94 [95% CI, −4.52, −1.36] mm Hg, p < 0.001). The reduction of daytime SBP (WMD 0.98 [95% CI, −0.20, 2.17] mm Hg, p = 0.10), DBP (WMD 0.11 [95% CI, −0.68, 0.89] mm Hg, p = 0.79), 24 hour SBP (WMD −0.75 [95% CI, −1.93, 0.42] mm Hg, p = 0.21) and DBP (WMD −0. 77 [95% CI, −1.55 0.01] mm Hg, p = 0.05) with bedtime dosing was similar with awakening dosing. ConclusionsBedtime dosing with ARBs is more effective in lowering sleep-time BP than awakening dosing in patients with essential hypertension, suggesting a utilization of chronotherapy of hypertension with ARBs to reduce sleep-time high BP. Larger multi-ethnic studies are needed to investigate the efficacy of chronotherapy of hypertension.

Blood pressure monitoring in sleep: time to wake up.

Hypertension is a highly common condition with well-established adverse consequences. Ambulatory blood pressure monitoring has repeatedly been shown to better predict cardiovascular outcomes and mortality, compared to single office visit blood pressure. Non-dipping of sleep-time blood pressure is an independent marker for increased cardiovascular risk. We review blood pressure variability and the challenges of blood pressure monitoring during sleep. Although pathological sleep such as obstructive sleep apnea has been associated with non-dipping of sleep-time blood pressure, blood pressure is not routinely measured during sleep due to lack of unobtrusive blood pressure monitoring technology. Second, we review existing noninvasive continuous blood pressure monitoring technologies. Lastly, we propose including sleep-time blood pressure monitoring during sleep studies and including sleep studies in patients undergoing ambulatory blood pressure monitoring.

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.

Asleep blood pressure: significant prognostic marker of vascular risk and therapeutic target for prevention.

Sleep-time blood pressure (BP) is a stronger risk factor for cardiovascular disease (CVD) events than awake and 24 h BP means, but the potential role of asleep BP as therapeutic target for diminishing CVD risk is uncertain. We investigated whether CVD risk reduction is most associated with progressive decrease of either office or ambulatory awake or asleep BP mean. We prospectively evaluated 18078 individuals with baseline ambulatory BP ranging from normotension to hypertension. At inclusion and at scheduled visits (mainly annually) during follow-up, ambulatory BP was measured for 48 consecutive hours. During the 5.1-year median follow-up, 2311 individuals had events, including 1209 experiencing the primary outcome (composite of CVD death, myocardial infarction, coronary revascularization, heart failure, and stroke). The asleep systolic blood pressure (SBP) mean was the most significant BP-derived risk factor for the primary outcome [hazard ratio 1.29 (95% CI) 1.22-1.35 per SD elevation, P < 0.001], regardless of office [1.03 (0.97-1.09), P = 0.32], and awake SBP [1.02 (0.94-1.10), P = 0.68]. Most important, the progressive attenuation of asleep SBP was the most significant marker of event-free survival [0.75 (95% CI 0.69-0.82) per SD decrease, P < 0.001], regardless of changes in office [1.07 (0.97-1.17), P = 0.18], or awake SBP mean [0.96 (0.85-1.08), P = 0.47] during follow-up. Asleep SBP is the most significant BP-derived risk factor for CVD events. Furthermore, treatment-induced decrease of asleep, but not awake SBP, a novel hypertension therapeutic target requiring periodic patient evaluation by ambulatory monitoring, is associated with significantly lower risk for CVD morbidity and mortality.

P5726Diabetes mellitus is associated with high sleep-time blood pressure and non-dipping pattern

P5726Diabetes mellitus is associated with high sleep-time blood pressure and non-dipping pattern

OP.3A.06] PROGRESSIVE DISRUPTION OF AMBULATORY BLOOD PRESSURE REGULATION WITH SEVERITY STAGE OF CHRONIC KIDNEY DISEASE

Objective: Sleep-time hypertension and the non-dipper blood pressure (BP) patterning determined by ambulatory BP monitoring (ABPM) are highly prevalent in chronic kidney disease (CKD), and both factors have been consistently associated with the elevated cardiovascular disease (CVD) risk of such patients. We have assessed the prevalence of these alterations in ambulatory BP regulation as a function of the severity stage of CKD among the participants of the Hygia Project, a research network presently composed of 292 investigators of 40 clinical sites, primarily designed, among other objectives, to evaluate the prognostic value of ABPM to predict CVD risk. Design and method: This cross-sectional investigation involved 7,452 patients with CKD (estimated glomerular filtration rate [eGFR] <60, albuminuria, or both, at least twice within 3 months), 4,325 men/3,127 women, 65.3 ± 13.8 years of age, with BP, according to ABPM criteria, ranging from normotension to sustained hypertension. Ambulatory BP was measured for 48 consecutive hours. Results: There was a highly significant (P < 0.001) progressive increase in the asleep systolic BP (SBP) mean with increasing severity of CKD. The awake SBP mean, however, did not changed consistently throughout the different stages of CKD. Accordingly, the sleep-time relative SBP decline was progressively and significantly (P < 0.001) attenuated towards a more non-dipper BP patterning with diminishing eGFR. Most important, the proportion of patients with the riser BP pattern (asleep SBP mean greater than awake SBP mean) significantly and progressively increased from 5.8% of the participants with stage-1-CKD to a very high 33.7% of the participants with stage-5-CKD. Conclusions: This study, the largest reported so far on CKD patients evaluated by highly-reproducible 48 h ABPM, documents the high prevalence of alteration in sleep-time BP regulation in this condition. Most important, prevalence of the riser BP pattern, associated with highest CVD risk, is also very high, from 20% in stage-3-CKD to 34% in end-stage-renal-disease. Collectively, these findings indicate ABPM should be mandatory for proper CVD risk stratification in CKD, as well as a means to establish the most adequate therapeutic scheme to properly control sleep-time BP and decrease CVD risk.

OP.4A.06] CARDIOVASCULAR RISK IS BETTER REDUCED BY BEDTIME THAN UPON AWAKENING HYPERTENSION TREATMENT-REGIMEN

Objective: In hypertension, ingesting blood pressure (BP)-lowering medications at bedtime, compared to upon awakening, is usually associated with significantly improved reduction of sleep-time BP mean, a sensitive prognostic marker of cardiovascular disease (CVD) risk. The Hygia Project, a research network presently composed of 292 investigators of 40 clinical sites, was specifically designed to test the hypothesis that bedtime chronotherapy entailing the entire daily dose of >1 conventional hypertension medications exerts better ambulatory BP control and CVD risk reduction than all such medications ingested upon awakening. Design and method: We conducted a prospective, randomized, open-label, blinded endpoint trial of 15,674 hypertensive patients (8,682 men/6,992 women, 60.4 ± 13.7 years of age) according to ambulatory BP (ABPM) criteria. Participants were randomized to ingest all their prescribed hypertension medications upon awakening (n = 7,848) or the entire daily dose of at least one of them at bedtime (n = 7,826). Among the later, 3,918 participants were ingesting all medications at bedtime and the remaining 3,908 ingested some medications at bedtime and others upon awakening. At inclusion and at every scheduled clinic visit for ABPM (at least annually) during follow-up, BP was assessed for 48 h. The primary CVD-outcome was the composite of CVD death, myocardial infarction, coronary revascularization, heart failure, and stroke. Results: During a median 5.1-year follow-up, we documented 1,154 major CVD events. Patients of the bedtime, compared with the upon-waking, treatment group showed significantly lower hazard ratio of CVD events, adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, cigarette smoking, HDL-cholesterol, asleep systolic BP (SBP) mean, sleep-time relative SBP decline, and previous CVD event (0.47 [95%CI 0.42–0.54], P < 0.001). CVD risk was further reduced among patients who ingested not just some, but all their BP-lowering medications at bedtime (0.27 [0.21–0.34], P < 0.001, compared with ingestion of all medications upon awakening). Conclusions: In hypertensive patients, ingestion of some (preferably all) BP-lowering medications at bedtime, compared with ingestion of all such medications upon-awakening, results in improved ambulatory BP control (significantly enhanced decrease of asleep BP and increase of sleep-time relative BP decline) and, most importantly, markedly reduced risk of major CVD events.

Ambulatory Blood Pressure Monitoring in the Diagnosis and Treatment of Hypertension.

Clinicians should take initiatives to establish ambulatory blood pressure monitoring (ABPM) services in their own practice, or to ensure that they have access to such services elsewhere. Whenever possible, ABPM should be performed in suitable cases, where it is likely to deliver clinically useful information for making a correct diagnosis, or for tailoring the anti-hypertensive treatment regimen for each individual patient. ABPM is clinically useful, among others, for identifying people with "masked normotension", "masked hypertension", "sleep-time hypertension", and "reduced decline of sleep-time blood pressure". This review briefly outlines the rationales for the use of ABPM, interpretations of the ABPM-derived parameters, and the advantages of ABPM in decision making in the management of hypertension.

Ambulatory blood pressure monitoring in diabetes for the assessment and control of vascular risk

The diagnosis of hypertension and the clinical decisions regarding its treatment are usually based on daytime clinic blood pressure (BP) measurements. However, the correlation between BP levels and target organ damage, cardiovascular (CV) risk, and long-term prognosis, is higher for ambulatory (ABPM) than clinic measurements, both in the general population as well as in patients with diabetes. Moreover, there is consistent evidence in numerous studies that the asleep BP better predicts CV events than either the awake or 24h means. The prevalence of abnormal BP pattern and sleep-time hypertension is extensive in diabetes, often leading to inaccurate diagnoses of hypertension and its therapeutic control in the absence of complete and careful assessment of the entire 24h, i.e., daytime and night-time, BP pattern. Accordingly, ABPM should be the preferred method to comprehensively assess and decide the optimal clinical management of patients with diabetes directed to properly reduce elevated sleep-time BP, which might also lead to a significant reduction of CV events.

Monitorización ambulatoria de la presión arterial en diabetes para valoración y control de riesgo vascular

The diagnosis of hypertension and the clinical decisions regarding its treatment are usually based on daytime clinic blood pressure (BP) measurements. However, the correlation between BP levels and target organ damage, cardiovascular (CV) risk, and long-term prognosis, is higher for ambulatory (ABPM) than clinic measurements, both in the general population as well as in patients with diabetes. Moreover, there is consistent evidence in numerous studies that the asleep BP better predicts CV events than either the awake or 24h means. The prevalence of abnormal BP pattern and sleep-time hypertension is extensive in diabetes, often leading to inaccurate diagnoses of hypertension and its therapeutic control in the absence of complete and careful assessment of the entire 24h, i.e., daytime and night-time, BP pattern. Accordingly, ABPM should be the preferred method to comprehensively assess and decide the optimal clinical management of patients with diabetes directed to properly reduce elevated sleep-time BP, which might also lead to a significant reduction of CV events.

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.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.

1C.05

Objective: The extent of blood pressure (BP) surge upon waking has been associated with increased cardiovascular (CVD) risk in some, but not all, studies. Numerous studies, however, have consistently shown the association between elevated sleep-time BP mean and the rising BP pattern with increased CVD risk, leading to a paradox, as patients with sleep-time hypertension or non-dipper/riser BP pattern have attenuated morning BP surge. We evaluated the comparative prognostic value for CVD events of the morning BP surge and sleep-time BP among the participants in the ongoing Hygia Project. Design and method: This study involved 11255 subjects, 6028 men/5227 women, 58.9 ± 14.5 years of age, 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 at 30-min intervals at night for 48 h. During monitoring, subjects maintained a diary listing the times of going to bed and awakening. Results: We documented 1539 total events, including 400 deaths, 176 strokes, 144 myocardial infarctions, 147 coronary revascularizations, and 193 heart failures. A greater prewaking systolic BP surge was associated with significantly lower, not higher, CVD risk in a Cox proportional-hazard model adjusted for the significant influential characteristics of age, sex, diabetes, chronic kidney disease, cigarette smoking, waist perimeter, and history of previous CVD event (hazard ratio [HR] 0.83 [95%CI 0.78–0.88] per each 1-SD increment; P < 0.001). The HR was progressively and significantly higher in the first three than in the last two quintiles of increasing prewaking BP surge. The prognostic value of morning surge markedly decreased after correcting by the asleep BP mean, the single most significant prognostic marked of total CVD events (HR = 1.37 [1.29–1.44], P < 0.001). Conclusions: Our findings document that, when properly analyzed as a continuous variable, a larger morning BP surge is associated with a significantly lower CVD risk, in line with the markedly greater risk associated with decreasing dipping of the BP pattern, and the most highly significant prognostic value of progressively elevated asleep BP, an independent prognostic marker of CVD risk that has also been prospectively validated as a relevant therapeutic target for CVD risk reduction.

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 chronic kidney disease

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 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.

Morning Surge and Sleep-Time Blood Pressure as Prognostic Markers of Cardiovascular Risk: The Hygia Project

Morning Surge and Sleep-Time Blood Pressure as Prognostic Markers of Cardiovascular Risk: The Hygia Project

Differing Prognostic Value of Sleep-Time and Awake-Time Blood Pressure Means in Normotensive Individuals: The Hygia Project

catheter was inserted (Simplicity Flex) inside the renal artery, allowing the delivery of radiofrequency energy to the renal artery innervation. Radiofrequency applications were performed within the main stem of the renal arteries, bilaterally, with a series of 6 applications, 60 s duration each. At the end of the procedure, renal arteriography was performed for evaluation of vascular integrity. Results: Data were obtained at baseline and monthly until 180th day of follow-up. Baseline values of blood pressure were 196/122 mmHg in the office, and 164/109 mmHg by 24h ABPM. The decreased of ABPM data was 47/38mmHg, achieving values of 117/71mmHg with 14 days after procedure (figure 1), with the same average at 180th day, reducing from 7 to 3 antihypertensive drugs in 6 months. The procedure was performed without complications. Conclusions: Renal sympathetic denervation using the irrigated radiofrequency ablation catheter was effective in a patient with resistant hypertension.

Around-the-clock ambulatory blood pressure monitoring is required to properly diagnose resistant hypertension and assess associated vascular risk.

Diagnosis of resistant hypertension (RH) is currently based upon awake-time office blood pressure (BP). An increasing number of studies have documented abnormally elevated sleep-time BP in most RH patients, indicating that diagnosis of true RH cannot be determined solely by comparison of office BP with either patient awake-time BP self-measurements or awake-BP mean from ambulatory monitoring (ABPM), as is customary in the published literature. Moreover, the ABPM-determined sleep-time BP mean is an independent and stronger predictor of cardiovascular and cerebrovascular disease (CVD) risk than either daytime office/ABPM-derived awake or 24-hour means. Results of the recently completed MAPEC (Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares) prospective outcomes study, which included a large cohort of RH patients, established that time of treatment relative to circadian rhythms constituted a critically important yet often neglected variable with respect to BP control. The study found that bedtime versus morning ingestion of the full dose of ≥1 BP-lowering medications resulted in both better therapeutic normalization of sleep-time BP and reduced CVD morbidity and mortality, including in RH patients. Accordingly, ABPM is highly recommended to properly diagnose and manage true RH, with a bedtime hypertension medication regimen as the therapeutic scheme of choice.