Nighttime Blood Pressure Decline Research Articles

NIGHTTIME BLOOD PRESSURE ASSESSED USING HOME MONITORING IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES/PREDIABETES: ASSOCIATION AND AGREEMENT WITH AMBULATORY MONITORING

Objective: To investigate the agreement between nighttime blood pressure (BP) measurements using home (HBPM) or ambulatory BP monitors (ABPM) in individuals with hypertension and type 2 diabetes mellitus (DM2) or prediabetes. Design and method: Adults with hypertension (treated or untreated) and DM2 or prediabetes underwent ABPM (measurements at 20 minutes intervals, Microlife WatchBP03) and HBPM (duplicate morning/evening measurements for 7 days, 3 nights with 3 measurements/night, Microlife WatchBP Home-N). Nighttime hypertension was defined as BP >= 120/70 mmHg (systolic/diastolic). Nighttime BP dipping was calculated as the ratio of nighttime BP decline to the daytime levels. Individuals with nighttime BP dip (systolic and/or diastolic) <10% were classified as non-dippers. Results: Data from 113 participants were analyzed (mean age [SD] 65±9.1 years, 67% men, body mass index 30.7±4.8 kg/m2, 84% with DM2, 22% cardiovascular disease, 94% treated hypertension). Average daytime HBPM was 129.2±13.2/73.3±7.8 mmHg and ABPM 126.7±12.1/72.5±7.4 mmHg (systolic/diastolic, p<0.01/p=NS), whilst nighttime HBPM was 115.3±13.1/63.6±7.6 mmHg and ABPM 113.9±13.4/63±7.1 mmHg (systolic/diastolic, p<0.05/p=NS). Strong correlation was observed between HBPM and ABPM levels: daytime r=0.71/0.74 and nighttime 0.86/0.78, systolic/diastolic, p<0.01)]. Good agreement was also found between ABPM and HBPM in diagnosing nighttime hypertension (81%/90%; kappa=0.55/0.70 systolic/diastolic). Among the participants, 32%/31% were classified as non-dippers (HBPM/ABPM, p=NS), with a 74% agreement (kappa=0.41) in detecting non-dippers. Conclusions: These preliminary findings indicate that in individuals with hypertension and DM2 or prediabetes, nighttime BP assessed by a novel home monitor is feasible and shows strong correlation and satisfactory agreement with reference ABPM in detecting nighttime hypertension and non-dipping.

The relationship between the prognostic nutritional index and non-dipping blood pressure pattern in patients with newly diagnosed hypertension

Aims: It has been suggested that immuno-nutritional status may play a role in blood pressure (BP) variations. This study aimed to investigate whether prognostic nutritional index (PNI) values differ between normotensive individuals and patients with newly diagnosed untreated hypertension (NDHT) and to clarify the relationship between the PNI and circadian BP patterns in NDHT patients.
 Methods: This retrospective study included 328 adult participants, comprising 164 NDHT patients and 164 normotensive individuals. The non-dipper BP pattern (NDP) was defined as a nighttime decline in BP of less than 10%. The PNI was calculated using the following formula: PNI=([10 × serum albumin (g/dL)] + [0.005 × total lymphocyte count]).
 Results: The mean PNI value was lower in the NDHT group than the normotensive group (53.6±6.1 vs. 58.2±5.3, p

Evaluation of the ability of a commercially available cuffless wearable device to track blood pressure changes.

Cuffless wearable blood pressure (BP) devices may allow detailed evaluation of BP for prolonged periods, but their ability to accurately track BP changes is uncertain. We investigated whether a commercially available cuffless wearable device tracks: 24-h systolic (SBP) and diastolic BP (DBP) compared to conventional ambulatory monitoring (ABPM); and antihypertensive medication-induced BP changes compared to cuff-based home BP monitoring (HBPM). We fitted 41 participants (32% females, 58 ± 14 years, 80% hypertensive) with a wrist-wearable cuffless BP device (Aktiia) continuously for 6-12 days. At the beginning and the end of this period, 24-h ABPM was performed. Three participants with hypertension (one female; 60 ± 8 years) wore the Aktiia device and performed HBPM continuously one week before and 2 weeks after antihypertensive medication uptitration. Compared to ABPM, Aktiia reported higher average SBP for 24-h (difference 4.9 mmHg, 95% CI [1.9, 7.9]) and night-time (15.5[11.8, 19.1] mmHg; all P ≤ 0.01), but similar daytime (1.0 [-1.8, 3.8] mmHg; P = 0.48). Similarly, average cuffless DBP was higher for 24-h (4.2 [2.3, 6.0] mmHg) and night-time (11.8 [9.5, 14.1] mmHg; both P < 0.001), but similar during daytime (1.4 [-0.4, 3.23] mmHg; P = 0.13). Aktiia also reported reduced night-time dip for SBP (difference 14.2 [12.1, 16.3] mmHg) and DBP (10.2 [8.5, 11.9] mmHg; both P < 0.001). The average medication-induced SBP/DBP decline after 2 weeks of uptitration was -1.0/-0.8 mmHg with Aktiia vs. -19.7/-11.5 mmHg with HBPM ( P = 0.03 for difference). This cuffless wearable device did not accurately track night-time BP decline and results suggested it was unable to track medication-induced BP changes.

Pheno-genotypical features of masked hypertension in athletes in the Republic of Sakha (Yakutia)

Objective. The aim of the study is to identify pathogenetic features of the development of masked hypertension in athletes in the Republic of Sakha (Yakutia). Design and methods . We enrolled 205 young men and males: 147 athletes with different orientations of training activity (cyclic sports and martial arts) and 58 control individuals without physical activity. All subjects underwent 24-hour blood pressure (BP) monitoring, anthropometry, echocardiography, assessment of central hemodynamics, and a genetic study. Results. Despite similar sports experience, 40,8 % athletes have masked hypertension, which is more common among athletes with the “master of sports” qualification ( χ 2 = 5,68, df = 1, p = 0,013) and does not depend on sport type ( χ 2 = 2,09, df = 1, p = 0,107). Athletes with masked hypertension showed nocturnal hypertension, decreased myocardial function, and a high rate of left ventricular structural remodeling. Conclusions. We identified the following genetic and phenotypic features: associations of gene polymorphisms responsible for the development of hypertension, episodes of insufficient nighttime BP decline, nocturnal hypertension, structural remodeling of the heart. These findings suggest that people with masked hypertension show cardiovascular overstrain at rest, which considering excessive physical load can lead to target-organ damage. This pathogenetic factors can be considered as phenogenotypic predictors of hypertension development and require further investigation.

Nighttime blood pressure decline as a predictor of renal injury in patients with hypertension: a population-based cohort study.

We explored whether the nighttime blood pressure (BP) decline predicts renal function decline in a population-based cohort with primary hypertension. We measured the baseline ambulatory BP and glomerular filtration rate (GFR) in a cohort of 1,042 primary hypertensive patients. We repeated the GFR measurements and calculated the rate of GFR decline after a median follow-up of 5.8 years. The estimated GFR (eGFR) declined by −0.23 to −0.20 mL/min per year as the nighttime systolic BP (SBP), diastolic BP (DBP), and mean BP decline rates increased by 1% (P < 0.001). In the fully adjusted model, the nighttime SBP, DBP, and mean BP were all related to a steeper rate of eGFR decline by −0.25 to −0.22 mL/min per 1% increase. The adjusted multivariable results indicated that the odds of an eGFR decline were reduced by 46% when the nighttime SBP decline rate increased by 1% (OR= 0.54, 95% CI: 0.46–0.62). The restricted cubic spline model indicated a non-linear dose-response relationship with the nighttime SBP, DBP, and mean BP. Nighttime BP may be an important biomarker of renal function injury in hypertensive patients.

Assessment of pupillary autonomic functions by dynamic pupillometry in different circadian arterial blood pressure patterns.

The aim of the present cross-sectional study was to evaluate the autonomic nervous system by dynamic pupillometry (DP) in normotensive and hypertensive individuals with either a non-dipper-type or a dipper-type circadian rhythm of blood pressure (BP). A total of 80 patients were allocated into four groups: normotensive/dipper (n=23), normotensive/nondipper (n=19), hypertensive/dipper (n=18), and hypertensive/nondipper (n=20). Pupil diameters (R0, R1, R2, and R%): latency (Lc), amplitude (Ac), velocity (Vc), and duration (Tc) of pupil contraction: latency (Ld), velocity (Vd), and duration (Td) of pupil dilatation were measured by DP. Among the DP parameters, Vc and Ac were known parasympathetic indices and R% was the major sympathetic index. Vc and Ac were higher in the dipper normotensives with respect to nondipper normotensives (Vc=5.19±0.85 vs. 4.58±0.71, P=0.017; Ac=1.66±0.27 vs. 1.49±0.28, P=0.048). Vc and Ac were higher in dipper hypertensives with respect to the nondipper subgroup of hypertensive cases (Vc=4.44±0.81 vs. 3.94±0.45, P=0.024; Ac=1.47±0.26 vs. 1.27±0.11, P=0.004). R% was higher in the nondipper subgroup of hypertensives than the dipper subgroup of hypertensive cases (36.7±4.8 vs. 33.5±3.8, P=0.033). Correlation analyses showed moderate positive correlations of night-time decline in BP with Vc (r=0.460, P=0.001) and Ac (r=0.420, P=0.001). There was also a negative correlation between night-time decline in BP and R% (r=-0.259, P=0.001). Nondipping in BP is associated with lower parasympathetic activity both in normotensive and in hypertensives cases. Furthermore, in the nondipper subgroup of hypertensive cases, there is higher sympathetic activity than the dipper subgroup.

Relationship between obstructive sleep apnea and markers of cardiovascular alterations in never-treated hypertensive patients

We addressed a question if there is a relationship between severity of newly diagnosed obstructive sleep apnea (OSA) and markers of cardiovascular alterations in middle-aged untreated hypertensive patients. In 121 consecutive patients with never-treated essential hypertension (mean age 35.9±10.1 years; 97 men and 24 women) evaluation of office and ambulatory blood pressure (BP) measurements, metabolic syndrome (MS) components and markers of alterations in cardiovascular system including left ventricular structure and function, carotid artery wall intima-media thickness (cIMT) and urinary albumin excretion (UAE) was performed. OSA was classified as mild (apnea/hypopnea index (AHI) 5-15 events h(-1)) or moderate-to-severe (AHI >15 events h(-1)). Mild and moderate-to-severe OSA were diagnosed in 30% and 20% of patients, respectively. No differences in nighttime BP levels and decline between patients with and without OSA were observed. The patients with moderate-to-severe OSA were characterized by higher cIMT (0.74±0.16 vs. 0.60±0.15 mm; P=0.001), UAE (14.5±6.9 vs. 10.0±8.0 mg 24 h(-1); P=0.014), relative wall thickness (0.42±0.05 vs. 0.39±0.05; P=0.023) and by a higher degree of diastolic dysfunction (E'-wave velocity 11.4±3.2 vs. 15.5±3.8 m s(-1); P<0.001) as compared with the patients without OSA. In multivariate analysis, AHI independently of BP and MS components correlated with UAE, relative wall thickness and E'-wave velocity. In the middle-aged never-treated hypertensive patients, moderate-to-severe OSA correlates with markers of cardiovascular alterations independently of BP levels and MS components.

Abnormalities in chronic kidney disease of ambulatory blood pressure 24 h patterning and normalization by bedtime hypertension chronotherapy

In chronic kidney disease (CKD), the prevalence of hypertension is very high, escalating with diminishing renal function. Typically, the diagnosis of hypertension and the clinical decisions regarding its treatment are based on daytime clinic blood pressure (BP) measurements. However, the correlation between BP level and target organ damage, cardiovascular risk and long-term prognosis is greater for ambulatory than clinic measurements. Moreover, evidence is consistent among numerous studies that the elevated risk and incidence of end-organ injury and fatal and non-fatal cardiovascular events are significantly associated with blunted night-time BP decline, and that the asleep BP better predicts cardiovascular events than either the awake or 24-h BP mean. The prevalence of abnormally high asleep BP is extensive in CKD, significantly increasing with its severity. In CKD, the diagnoses of hypertension and its therapeutic control are often inaccurate in the absence of complete and careful assessment of the entire 24 h, i.e. daytime and night-time, BP pattern. Accordingly, ambulatory BP monitoring should be the preferred method to comprehensively assess and decide the optimal clinical management of patients with CKD. Recent findings indicate therapeutic restoration of normal physiologic BP reduction during night-time sleep is the most significant independent predictor of decreased cardiovascular and cerebrovascular risk, both in patients with and without CKD, and is best achieved when antihypertensive medications, mainly those blocking the renin-angiotensin-aldosterone system, are routinely taken at bedtime.

PP120-MON RELATIONSHIP BETWEEN SERUM ALBUMIN LEVELS, AS A BIOMARKER OF NUTRITIONAL STATUS, AND NOCTURNAL DECLINE OF BLOOD PRESSURE IN ELDERLY PATIENTS

Rationale: Serum albumin levels are one of indicators for evaluating nutritional status and correlate negatively with C-reactive protein levels, a risk marker of inflammatory process of vascular atherogenesis, affecting circadian blood pressure (BP) rhythm. However, how serum albumin influences nighttime BP decline, which is the crucial predictor of cardiovascular events through vascular atherosclerosis, is not yet fully understood. We evaluated the relation between 24hour BP and serum albumin levels in elderly patients. Methods: Patients, who fulfilled the following enrollment criteria: 70 years old and above, estimated glomerular filtration rate >30mL/min/1.73m2, systolic and diastolic BP 0.05) with sleeping/waking mean BP ratios. Conclusion: Our findings suggest that serum albumin and total cholesterol in the elderly patients related to loss of the nocturnal BP decline, a predictor of cardiovascular organ damages. This suggests that poor nutrition has a higher cardiovascular risk and death.

Recomendaciones 2013 para el uso de la monitorización ambulatoria de la presión arterial para el diagnóstico de hipertensión en adultos, valoración de riesgo cardiovascular y obtención de objetivos terapéuticos (resumen). Recomendaciones conjuntas de la International Society for Chronobiology (ISC), American Association of Medical Chronobiology and Chronotherapeutics (AAMCC), Sociedad Española de Cronobiología Aplicada, Cronoterapia y Riesgo Vascular (SECAC), Sociedad Española de

Correlation between systolic (SBP) and diastolic (DBP) blood pressure (BP) level and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is much greater for ambulatory BP monitoring (ABPM) than daytime office measurements. The 2013 ABPM guidelines specified herein are based on ABPM patient outcomes studies and constitute a substantial revision of current knowledge. The asleep SBP mean and sleep-time relative SBP decline are the most significant predictors of CVD events, both individually as well as jointly when combined with other ABPM-derived prognostic markers. Thus, they should be preferably used to diagnose hypertension and assess CVD and other associated risks. Progressive decrease by therapeutic intervention in the asleep BP mean is the most significant predictor of CVD event-free interval. The 24 h BP mean is not recommended to diagnose hypertension because it disregards the more valuable clinical information pertaining to the features of the 24 h BP pattern. Persons with the same 24 h BP mean may display radically different 24 h BP patterns, ranging from extreme-dipper to riser types, representative of markedly different risk states. Classification of individuals by comparing office with either the 24 h or awake BP mean as “masked normotensives” (elevated clinic BP but normal ABPM), which should replace the terms of “isolated office” or “white-coat hypertension”, and “masked hypertensives” (normal clinic BP but elevated ABPM) is misleading and should be avoided because it disregards the clinical significance of the asleep BP mean. Outcome-based ABPM reference thresholds for men, which in the absence of compelling clinical conditions are 135/85 mmHg for the awake and 120/70 mmHg for the asleep SBP/DBP means, are lower by 10/5 mmHg for SBP/DBP in uncomplicated, low-CVD risk, women and lower by 15/10 mmHg for SBP/DBP in male and female high-risk patients, e.g., with diabetes, chronic kidney disease (CKD), and/or past CVD events. In the adult population, the combined prevalence of masked normotension and masked hypertension is >35%. Moreover, >20% of “normotensive” adults have a non-dipper BP profile and, thus, are at relatively high CVD risk. Clinic BP measurements, even if supplemented with home self-measurements, are unable to quantify 24 h BP patterning and asleep BP level, resulting in potential misclassification of up to 50% of all evaluated adults. ABPM should be viewed as the new gold standard to diagnose true hypertension, accurately assess consequent tissue/organ, maternal/fetal, and CVD risk, and individualize hypertension chronotherapy. ABPM should be a priority for persons likely to have a blunted nighttime BP decline and elevated CVD risk, i.e., those who are elderly and obese, those with secondary or resistant hypertension, and those diagnosed with diabetes, CKD, metabolic syndrome, and sleep disorders.

2013 Ambulatory Blood Pressure Monitoring Recommendations for the Diagnosis of Adult Hypertension, Assessment of Cardiovascular and other Hypertension-associated Risk, and Attainment of Therapeutic Goals

Correlation between systolic (SBP) and diastolic (DBP) blood pressure (BP) level and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is much greater for ambulatory BP monitoring (ABPM) than daytime office measurements. The 2013 ABPM guidelines specified herein are based on ABPM patient outcomes studies and constitute a substantial revision of current knowledge. The asleep SBP mean and sleep-time relative SBP decline are the most significant predictors of CVD events, both individually as well as jointly when combined with other ABPM-derived prognostic markers. Thus, they should be preferably used to diagnose hypertension and assess CVD and other associated risks. Progressive decrease by therapeutic intervention of the asleep BP mean is the most significant predictor of CVD event-free interval. The 24-h BP mean is not recommended to diagnose hypertension because it disregards the more valuable clinical information pertaining to the features of the 24-h BP pattern. Persons with the same 24-h BP mean may display radically different 24-h BP patterns, ranging from extreme-dipper to riser types, representative of markedly different risk states. Classification of individuals by comparing office with either the 24-h or awake BP mean as “masked normotensives” (elevated clinic BP but normal ABPM), which should replace the terms of “isolated office” or “white-coat hypertension”, and “masked hypertensives” (normal clinic BP but elevated ABPM) is misleading and should be avoided because it disregards the clinical significance of the asleep BP mean. Outcome-based ABPM reference thresholds for men, which in the absence of compelling clinical conditions are 135/85 mmHg for the awake and 120/70 mmHg for the asleep SBP/DBP means, are lower by 10/5 mmHg for SBP/DBP in uncomplicated, low-CVD risk, women and lower by 15/10 mmHg for SBP/DBP in male and female high-risk patients, e.g., with diabetes, chronic kidney disease (CKD), and/or past CVD events. In the adult population, the combined prevalence of masked normotension and masked hypertension is >35%. Moreover, >20% of “normotensive” adults have a non-dipper BP profile and, thus, are at relatively high CVD risk. Clinic BP measurements, even if supplemented with home self-measurements, are unable to quantify 24-h BP patterning and asleep BP level, resulting in potential misclassification of up to 50% of all evaluated adults. ABPM should be viewed as the new gold standard to diagnose true hypertension, accurately assess consequent tissue/organ, maternal/fetal, and CVD risk, and individualize hypertension chronotherapy. ABPM should be a priority for persons likely to have a blunted nighttime BP decline and elevated CVD risk, i.e., those who are elderly and obese, those with secondary or resistant hypertension, and those diagnosed with diabetes, CKD, metabolic syndrome, and sleep disorders. (Author Correspondence: rhermida@uvigo.es or prf@unife.it).

Analysis of 24-hour ambulatory blood pressure monitoring in patients with diabetic nephropathy: a hospital-based study

The present study was designed to characterize and compare the ambulatory blood pressure changes of patients with Type 2 diabetic nephropathy (DN) and non-diabetic chronic kidney disease (CKD), and to investigate the features of ambulatory blood pressure in patients with Type 2 diabetic nephropathy (DN) in comparison with those of non-diabetic chronic kidney disease (CKD) in our medical center. 62 patients with Type 2 diabetic nephropathy (DN) in compliance with the diagnosis criteria of CKD were enrolled in the study, without renal replacement therapy. Their 24-h ambulatory blood pressure monitoring (ABPM) results were observed and compared with the ambulatory blood pressure results of 152 non-diabetic CKD patients with matching age, sex, renal function and other aspects. Analysis of ABPM data from 62 patients with Type 2 DN and 152 patients with nondiabetic CKD indicated: 1. The average 24-h systolic blood pressure (SBP), daytime and nighttime systolic blood pressure (SBP) in the patients with DN were all significantly higher than those of patients with non-DN. 2. Blood pressure variability did not differ considerably between the two groups; nighttime blood pressure decline was small in both groups, but not significantly different. 3. The systolic blood pressure loads in the patients with DN were all significantly higher than those of patients with non-DN. 4. The prevalence of abnormal Circadian BP rhythm was 90.3% in patients with DN, which did not differ considerably from the patients with non-DN represented by 81.6%. 5. The nighttime SBP was correlated with 24-h urinary protein in patients with both non-DN and DN. Systolic blood pressure control of patients with intermediate or advanced diabetic nephropathy was worse than that of patients with non-diabetic CKD, and non-dipping rhythm was quite common. The nighttime SBP correlated with 24-h urinary protein excretion.

Treatment-Time Regimen of Hypertension Medications Significantly Affects Ambulatory Blood Pressure and Clinical Characteristics of Patients With Resistant Hypertension

Patients with resistant hypertension (RH) are at greater risk for stroke, renal insufficiency, and cardiovascular disease (CVD) events than are those for whom blood pressure (BP) is responsive to and well controlled by therapeutic interventions. Although all chronotherapy trials have compared the effects on BP regulation of full daily doses of medications when ingested in the morning versus at bedtime, prescription of the same medications in divided doses twice daily (BID) is frequent. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and laboratory medicine parameters of RH patients evaluated by 48-h ambulatory BP monitoring (ABPM). This cross-sectional study evaluated 2899 such patients (1701 men/1198 women), 64.2 ± 11.8 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 1084 were ingesting all hypertension medications upon awakening (upon-awakening regimen), 1436 patients were ingesting the full daily dose of ≥1 of them at bedtime (bedtime regimen), and 379 were ingesting split doses of ≥1 medications BID upon awakening and at bedtime (BID regimen). Patients of the bedtime regimen compared with the other two treatment-time regimens had lower likelihood of microalbuminuria and chronic kidney disease; significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; plus higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. The bedtime regimen was also significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than the upon-awakening and BID regimens. The sleep-time relative SBP and DBP decline was significantly attenuated by the upon-awakening and BID regimens (p < .001), resulting in significantly higher prevalence of non-dipping in these two treatment-time regimen groups (80.5% and 77.3%, respectively) than in the bedtime regimen (54.4%; p < .001 between groups). Additionally, the prevalence of the riser BP pattern, associated with highest CVD risk, was much greater, 31.0% and 29.8%, respectively, among patients of the upon-awakening and BID-treatment regimens, compared with the bedtime regimen (17.6%; p < .001 between groups). Patients of the bedtime regimen also showed significantly higher prevalence of properly controlled ambulatory BP (p < .001) as a result of a greater proportion of them showing complete control of asleep SBP and DBP means. Our findings demonstrate significantly lower asleep SBP and DBP means and attenuated prevalence of blunted nighttime BP decline, i.e., lower prevalence of CVD risk markers, in RH patients ingesting the full daily dose of ≥1 hypertension medications at bedtime than in those ingesting all of them upon awakening or ≥1 of them as split doses BID. In RH, ingesting the same medications BID neither improves ambulatory BP control nor reduces the prevalence of non-dipping, and cannot be considered chronotherapy. Collectively, findings of this study indicate that a bedtime hypertension medication regimen, in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of true RH and avoid treatment-induced nocturnal hypotension, should be the therapeutic scheme of choice for patients who, by conventional cuff methods (and in the absence of ABPM) and the morning-treatment regimen, have been mistakenly judged to be resistant to therapy. (Author correspondence: rhermida@uvigo.es)

Administration-Time-Dependent Effects of Hypertension Treatment on Ambulatory Blood Pressure in Patients With Chronic Kidney Disease

Many published prospective trials have reported clinically 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 designed to evaluate prospectively 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)

Effects of Time-of-Day of Hypertension Treatment on Ambulatory Blood Pressure and Clinical Characteristics of Patients With Type 2 Diabetes

Generally, hypertensive patients ingest all their blood pressure (BP)-lowering agents in the morning. However, many published prospective trials have reported clinically meaningful morning-evening, treatment-time differences in BP-lowering efficacy, duration of action, and safety of most classes of hypertension medications, and it was recently documented that routine ingestion of ≥1 hypertension medications at bedtime, compared with ingestion of all of them upon awakening, significantly reduces cardiovascular disease (CVD) events. Non-dipping (<10% decline in asleep relative to awake BP mean), as determined by ambulatory BP monitoring (ABPM), is frequent in diabetes and is associated with increased CVD risk. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and analytical parameters of hypertensive patients with type 2 diabetes evaluated by 48-h ABPM. This cross-sectional study involved 2429 such patients (1465 men/964 women), 65.9 ± 10.6 (mean ± SD) yrs of age, enrolled in the Hygia Project, involving primary care centers of northwest Spain and designed to evaluate prospectively CVD risk by ABPM. Among the participants, 1176 were ingesting all BP-lowering medications upon awakening, whereas 1253 patients were ingesting ≥1 medications at bedtime. Among the latter, 336 patients were ingesting all BP-lowering medications at bedtime, whereas 917 were ingesting the full daily dose of some hypertension medications upon awakening and the full dose of others at bedtime. Those ingesting ≥1 medications at bedtime versus those ingesting all medications upon awakening had lower likelihood of metabolic syndrome and chronic kidney disease (CKD); had significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; and had higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. Moreover, patients ingesting all medications at bedtime had lowest fasting glucose, serum creatinine, uric acid, and prevalence of proteinuria and CKD. Ingestion of ≥1 medications at bedtime was also significantly associated with lower asleep systolic (SBP) and diastolic BP (DBP) means than treatment with all medications upon awakening. Sleep-time relative SBP and DBP 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 (68.6%) than when ≥1 of them was ingested at bedtime (55.8%; p < .001 between groups), and even further attenuated (49.7%) when all of them were ingested at bedtime (p < .001). Additionally, prevalence of the riser BP pattern, associated with highest CVD risk, was much greater (23.6%) among patients ingesting all medications upon awakening, compared with those ingesting some (20.0%) or all medications at bedtime (12.2%; p < .001 between groups). The latter group also showed 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 mean and attenuated prevalence of a blunted nighttime BP decline, i.e., lower prevalence of markers of CVD risk, and improved metabolic profile in patients with type 2 diabetes 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 type 2 diabetes. (Author correspondence: rhermida@uvigo.es)

Influence of Age and Hypertension Treatment-time on Ambulatory Blood Pressure in Hypertensive Patients

Some studies based on ambulatory blood pressure (BP) monitoring (ABPM) have reported a reduction in sleep-time relative BP decline towards a more non-dipping pattern in the elderly, but rarely have past studies included a proper comparison with younger subjects, and no previous report has evaluated the potential role of hypertension treatment time on nighttime BP regulation in the elderly. Accordingly, we evaluated the influence of age and time-of-day of hypertension treatment on the circadian BP pattern assessed by 48-h ABPM. This cross-sectional study involved 6147 hypertensive patients (3108 men/3039 women), 54.0 ± 13.7 (mean ± SD) yrs of age, with 2137 (978 men/1159 women) being ≥60 yrs of age. At the time of study, 1809 patients were newly diagnosed and untreated, and 4338 were treated with hypertension medications. Among the later, 2641 ingested all their prescribed BP-lowering medications upon awakening, whereas 1697 ingested the full daily dose of ≥1 hypertension medications at bedtime. Diagnosis of hypertension in untreated patients was based on ABPM criteria, specifically an awake systolic (SBP)/diastolic (DBP) BP mean ≥135/85 mm Hg and/or an asleep SBP/DBP mean ≥120/70 mm Hg. Collectively, older in comparison with younger patients were more likely to have diagnoses of microalbuminuria, chronic kidney disease, obstructive sleep apnea, metabolic syndrome, anemia, and/or obesity. In addition, the group of older vs. younger patients had higher glucose, creatinine, uric acid, triglycerides, and fibrinogen, but lower cholesterol, hemoglobin, and estimated glomerular filtration rate. In older compared with younger patients, ambulatory SBP was significantly higher and DBP significantly lower (p < .001), mainly during the hours of nighttime sleep and initial hours after morning awakening. The prevalence of non-dipping was significantly higher in older than younger patients (63.1% vs. 41.1%; p < .001). The largest difference between the age groups was in the prevalence of a riser BP pattern, i.e., asleep SBP mean greater than awake SBP mean (19.9% vs. 4.9% in older vs. younger patients, respectively; p < .001). The sleep-time relative SBP decline was mainly unchanged until ∼40 yrs of age, and then significantly and progressively decreasing with increasing age at a rate of .28%/yr (p < .001), reaching a minimum value of 4.38% ± .47% for patients ≥75 yrs of age. Treated compared with untreated patients showed lower awake and asleep SBP means, although the predictable changes of SBP and DBP with age were equivalent in both groups. As a consequence, there were no significant differences between untreated and treated patients in the changes of the sleep-time relative SBP and DBP declines with age. Additionally, the asleep SBP and DBP means were significantly lower and the sleep-time relative SBP and DBP declines significantly higher at all ages in patients ingesting ≥1 BP-lowering medications at bedtime as compared with those ingesting all medications upon awakening. Our findings document a significantly elevated prevalence of a blunted nighttime BP decline with increasing age ≥40 yrs. The prevalence of a riser BP pattern, associated with highest cardiovascular risk among all possible BP patterns, was 4 times more prevalent in patients ≥60 yrs of age than those <60 yr of age. Most important, there was an attenuated prevalence of a blunted nighttime BP decline at all ages when ≥1 hypertension medications were ingested at bedtime as compared with when all of them were ingested upon awakening. These findings indicate that older age should be included among the conditions for which ABPM is recommended for proper cardiovascular risk assessment. (Author correspondence: rhermida@uvigo.es)

Blunted Sleep-Time Relative Blood Pressure Decline Increases Cardiovascular Risk Independent of Blood Pressure Level—The “Normotensive Non-dipper” Paradox

Numerous studies have consistently shown an association between blunted sleep-time relative blood pressure (BP) decline (non-dipping) and increased cardiovascular disease (CVD) risk in hypertension. Normotensive persons with a non-dipper BP profile also have increased target organ damage, namely, increased left ventricular mass and relative wall thickness, reduced myocardial diastolic function, increased urinary albumin excretion, increased prevalence of diabetic retinopathy, and impaired glucose tolerance. It remains a point of contention, however, whether the non-dipper BP pattern or just elevated BP, alone, is the most important predictor of advanced target organ damage and future CVD events. Accordingly, we investigated the role of dipping status and ambulatory BP level as contributing factors for CVD morbidity and mortality in the MAPEC (Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares, i.e., Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Events) study. We prospectively studied 3344 individuals (1718 men/1626 women), 52.6 ± 14.5 (mean ± SD) yrs of age, during a median follow-up of 5.6 yrs. BP was measured by ambulatory monitoring (ABPM) for 48 h at baseline, and again annually or more frequently (quarterly) if treatment adjustment was required in treated hypertensive patients. At baseline, those with ABPM-substantiated hypertension were randomized to one of two treatment-time regimen groups: (i) ingestion of all prescribed hypertension medications upon awakening or (ii) ingestion of the entire dose of ≥1 of them at bedtime. Those found to be normotensive at baseline were untreated but followed and evaluated by repeated ABPM like the hypertensive patients. Participants were divided into four investigated categories on the basis of dipping status and ambulatory BP: (i) dipper vs. non-dipper, and (ii) normal ambulatory BP if the awake systolic (SBP)/diastolic (DBP) BP means were <135/85 mm Hg and the asleep SBP/DBP means were <120/70 mm Hg, and elevated ambulatory BP otherwise. Cox survival analyses, adjusted for significant confounding variables, documented that non-dippers had significantly higher CVD risk than dippers, whether they had normal (p = .017) or elevated ambulatory BP (p < .001). Non-dippers with normal awake and asleep SBP and DBP means, who accounted for 21% of the studied population, had similar hazard ratio (HR) of CVD events (1.61 [95% confidence interval, CI: 1.09–2.37]) as dippers with elevated ambulatory BP (HR: 1.54 [95% CI: 1.01–2.36]; p = .912 between groups). These results remained mainly unchanged for treated and untreated patients analyzed separately. Our findings document that the risk of CVD events is influenced not only by ambulatory BP elevation, but also by blunted nighttime BP decline, even within the normotensive range, thus supporting ABPM as a requirement for proper CVD risk assessment in the general population. The elevated CVD risk in “normotensive” individuals with a non-dipper BP profile represents a clear paradox, as those persons do not have “normal BP” or low CVD risk. Our findings also indicate the need to redefine the concepts of normotension/hypertension, so far established on the unique basis of BP level, mainly if not exclusively measured at the clinic, independently of circadian BP pattern. (Author correspondence: rhermida@uvigo.es)

The relationship between circadian blood pressure pattern and ventricular repolarization dynamics assessed by QT dynamicity

The aim of the present cross-sectional study was to evaluate ventricular repolarization dynamics by QT dynamicity in normotensive and hypertensive individuals with either a non-dipper-type or a dipper-type circadian rhythm of blood pressure (BP). A total of 103 patients were allocated into four groups as follows: (i) normotensive/dipper, n=28; (ii) normotensive/nondipper, n=26; (iii) hypertensive/dipper, n=25; and (iv) hypertensive/nondipper, n=24. The linear regression slopes of the QT interval measured to the apex and to the end of the T wave plotted against R-R intervals (QTapex/R-R and QTend/R-R slopes, respectively) were calculated from 24-h ambulatory ECG recordings using a dedicated algorithm. QTapex/R-R and QTend/R-R slopes were higher in the nondipper subgroup of normotensive cases with respect to the dipper subgroup of normotensive cases (QTapex/R-R=0.171±0.017 vs. 0.127±0.023, P=0.001; QTend/R-R=0.159±0.015 vs. 0.133±0.025, P=0.001). QTapex/R-R and QTend/R-R slopes were higher in the nondipper subgroup of hypertensive cases with respect to the dipper subgroup of hypertensive cases (QTapex/R-R=0.187±0.019 vs. 0.133±0.019, P=0.001; QTend/R-R=0.183±0.018 vs. 0.147±0.022, P=0.001). Pearson's correlation analyses revealed a higher negative correlation between night-time decline in BP and QTapex/R-R (r=-0.638, P=0.001). There was also a moderate negative correlation between night-time decline in BP and QTend/R-R (r=-0.504, P=0.001). The correlation coefficients for degree of night-time dipping and QT dynamicity indices were higher in hypertensive groups than in the normotensive groups. Blunting of the nocturnal fall in BP associates with impaired QT dynamicity indices in both normotensive and hypertensive groups.

Relationship Between Metabolic Syndrome, Circadian Treatment Time, and Blood Pressure Non-Dipping Profile in Essential Hypertension

There is a strong association between metabolic syndrome (MS) and increased cardiovascular risk. Moreover, elevated nighttime blood pressure (BP) and non-dipping (subjects with <10% decline in the asleep relative to the awake BP mean) have been also linked to increased cardiovascular morbidity and mortality. We investigated the relation between MS, circadian time of hypertension treatment, and impaired nighttime BP decline in a cross-sectional study on 3352 (1576 men/1776 women) non-diabetic hypertensive subjects, 53.7 ± 13.1 (mean ± SD) yrs of age. Among them, 2056 were ingesting all their prescribed hypertension medication upon awakening, and 1296 were ingesting at least one of their BP medications at bedtime. BP was measured by ambulatory monitoring for 48 consecutive hours to substantiate reproducibility of the dipping pattern. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate mean BP when awake and asleep for each subject. MS was present in 52.6% of the subjects. The prevalence of an altered non-dipper BP profile was significantly higher among subjects with MS (52.0% vs. 39.5% in subjects without MS, p < .001). Non-dipping was significantly more prevalent among subjects ingesting all BP-lowering medications upon awakening (56.8%) than among those ingesting at least one of their BP medications at bedtime (29.1%; p < .001). Subjects with MS had significantly higher values of uric acid (6.0 vs. 5.3 mg/dL, p < .001), plasma fibrinogen (331 vs. 315 mg/dL, p < .001), and erythrocyte sedimentation rate (14.8 vs. 12.4 mm, p < .001). Non-dipping was significantly associated with the presence of MS and treatment upon awakening in a multiple logistic regression model adjusted by significant confounding factors, including age, creatinine, erythrocyte sedimentation rate, and cigarette smoking. This cross-sectional study documents a significant increase of a blunted sleep-time BP decline in treated hypertensive subjects with MS. Even in the presence of MS, treatment at bedtime is significantly associated with lower prevalence of a high-risk non-dipper BP profile. (Author correspondence: rhermida@uvigo.es)

Low life purpose and high hostility are related to an attenuated decline in nocturnal blood pressure.

An attenuation of the nighttime decline in blood pressure (BP) predicts cardiovascular disease and cardiovascular-related mortality, beyond daytime BP levels. We investigated whether positive and negative psychological attributes were associated with sleep-wake BP ratios and examined sleep parameters as potential mediators of these relationships. Two hundred twenty-four participants (50% men; 43% Black; mean age = 60 years) underwent ambulatory BP monitoring for 2 days and nights. Self-reports of positive and negative psychological attributes were collected. In-home polysomnography was conducted for 2 nights, and a wrist actigraph was worn for 9 nights. Sleep-wake mean arterial pressure (MAP) ratios. After adjustment for demographics, body mass index, and hypertensive status, low life purpose and high hostility were associated with high sleep-wake MAP ratios. Depression, anxiety, and optimism were not related to MAP ratios. Sleep latency, fragmentation, architecture, and the apnea-hypopnea index were examined as potential mediators between psychological attributes and MAP ratios; only long sleep latency mediated the relationship between hostility and MAP ratios. Low life purpose and high hostility are associated with high sleep-wake BP ratios in Black and White adults, and these relationships are largely independent of sleep.