We propose a new vector index for the statistical assessment of antihypertensive treatment duration and homogeneity from ambulatory blood pressure monitoring. We termed this approach for evaluating and comparing blood pressure coverage offered by antihypertensive drugs over 24 h as the reduction-duration-homogeneity index. The reduction-duration-homogeneity index is a three-component vector index that incorporates information about the reduction, duration, and homogeneity of antihypertensive treatment, as well as their statistical significance. The advantages of the reduction-duration-homogeneity index are demonstrated by several comparative examples.

Population-based epidemiology and clinical case studies document a prominent 24-hour pattern in the occurrence of silent and non-silent angina pectoris (AP), acute myocardial infarction (AMI), and sudden cardiac death (SCD). When the data are summarized per 3 - 6 hour intervals of the 24 hours, the temporal pattern of these ischemic heart disease (IHD) events shows a single morning peak between 06: 00 and 12:00 h in incidence. However, when the occurrence of such events is examined according to the hour of their occurrence, several studies reveal a second late-afternoon/early-evening minor peak. The true day - night pattern in AP, AMI, and SCD is unknown because the data represent nothing more than the recorded `"time of day'' of the events. It has been postulated that the day - night pattern in IHD events is at least in part dependent on endogenous circadian rhythms, which are synchronized by the daily routine of sleep in darkness/ activity in light. Approximately 20% of the working population is involved in night and rotating shift employment; thus, "time of day'' studies are not likely to accurately represent the actual "chronorisk'' of vulnerable individuals to IHD events. Moreover, it is likely that the events in the persons comprising the population and clinical case studies were influenced by ongoing treatment with antihypertensive, anticoagulant, and antianginal medications. Details regarding the class, dose, and schedule of such medications are rarely if ever reported in accounts of IHD events. Many of the investigations were conducted decades ago, when short-acting antihypertensive and cardiovascular medications required twice or thrice-a-day dosing, and thus the observed day - night variations could be significantly affected by such multiple treatment timings each day. Thus, the magnitude and nature (single versus multiple peaks) of the reported day - night patterns in AP, AMI, and SCD are suspect, as are their geneses. Presently, it is hypothesized that multiple cyclic exogenous triggers (e. g. posture, physical exertion, emotional stress, and medication scheduling) superimposed upon an endogenous 24-hour susceptibility-resistance pattern that arises from circadian rhythms in heart rate, blood pressure, rate-pressure product, and haemostasis, are major contributory factors.

Summary: Background: Peroxisome proliferator-activated receptor-γ (PPARγ) ligands were shown to induce the vascular endothelial growth factor (VEGF) synthesis in several cell types. We tested the effect of ciglitazone, one of the most specific PPARγ agonists, on the angiogenic activity of VEGF. Methods: Experiments were performed on human umbilical vein endothelial cell (HUVEC), incubated for 12 to 48 h with human VEGF165 (30 ng/ml) in the presence or absence of ciglitazone (1 – 10 µM). Cell proliferation was tested by BrdU incorporation. Migration was measured in modified Boyden chambers. Morphogenesis and capillary outgrowth were assessed by tube formation assay and spheroid cell culture, respectively. Results: Treatment with ciglitazone inhibited by about 50 % VEGF-induced proliferation, migration, morphogenesis, and sprouting of capillaries. Conclusions: Thus we conclude that, despite augmentation of VEGF generation, ciglitazone may act as an antiangiogenic agent attenuating VEGF activity by directly influencing endothelial cells. Zusammenfassung: Grundlagen: Peroxisome proliferator-activated receptor-γ (PPARγ)-Liganden induzieren die Synthese von Vascular Endothelial Growth Factor (VEGF) in verschiedenen Zellen. Methodik: Es wurde die Wirkung von Ciglitazon, einer der potentesten PPARγ-Agonisten, auf die angiogenetische Wirkung von VEGF untersucht. HUVEC (human umblical endothelial cells) wurden für 12 bis 48 Stunden mit humanem VEGF165 (30 ng/ml) sowohl mit, als auch ohne Ciglitazon (1 – 10 µM) inkubiert. Ergebnisse: Ciglitazon hat die angiogenetischen Aktivitäten von Endothelzellen gehemmt. Die Behandlung mit Ciglitazon hat die VEGF-induzierte Proliferation und Migration von HUVEC unterdrückt. Weiteres konnte mit der Ciglitazon-Behandlung eine Reduktion der morphogenetischen Kapazität von Endothelzellen („tube formation assay”) sowie ein vermindertes Aussprossen der Kapillaren (Sphärenzellkultur) nachgewiesen werden. Schlußfolgerungen: Obwohl Ciglitazon die Synthese von VEGF erhöht, hat Ciglitazon eine anti-angiogenetische Wirkung, welche durch Hemmung der VEGF-Aktivität und direkten Einfluß auf Endothelzellen bedingt ist.

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.

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.

The activity of heme oxygenase enzymes (HOs) is responsible for the endogenous source of carbon monoxide (CO). Their activities can be inhibited by tin protoporphyrin-IX (SnPPIX). Recent data indicate the involvement of HOs in the regulation of angiogenesis. Here, we investigated the role of the HO pathway in the production and angiogenic activity of vascular endothelial growth factor (VEGF) in endothelial cells treated with SnPPIX, or cultured in the presence of a CO-releasing molecule (CO-RM). Addition of CO-RM or induction of HO-1 by hemin resulted in a threefold elevation in CO production in culture medium (up to 20.3 microg/L) and was associated with a 30% increase in VEGF synthesis. Much higher levels of CO (up to 60 microg/L) and a further increase in VEGF production (by 277%) were measured in cells treated with prostaglandin-J(2), a potent activator of HO-1. SnPPIX prevented the induction of CO generation and inhibited VEGF synthesis. Moreover, SnPPIX reduced the VEGF-elicited angiogenic activities of endothelial cells by decreasing their proliferation (by 26%), migration (by 46%), formation of tubes on Matrigel (by 48%), and outgrowth of capillaries from endothelial spheroids (by 30%). In contrast, overexpression of HO-1 or incubation of cells with CO-RM led to an increase in capillary sprouting. Thus, HO activity up-regulates VEGF production and augments the capability of endothelial cells to respond to exogenous stimulation.

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.

Heme oxygenase-1 (HO-1), an inducible enzyme degrading heme to biliverdin, iron and carbon monoxide, is involved in regulation of inflammation and angiogenesis. Tin protoporphyrin (SnPPIX) and zinc protoporphyrin (ZnPPIX) are commonly used as competitive inhibitors of HO-1. We aimed to compare the effects of SnPPIX and ZnPPIX on the production of vascular endothelial growth factor (VEGF), activity of inducible nitric oxide synthase (iNOS) and cell viability. All experiments were performed on rat vascular smooth muscle cells and murine RAW264.7 macrophages treated with 3-10 microM protoporphyrins. Some cells were additionally stimulated with IL-1beta or with lipopolysaccharide. After a 24 h incubation period SnPPIX and ZnPPIX significantly reduced the generation of VEGF in vascular smooth muscle cells and RAW264.7, both in resting and stimulated cells. The inhibitory potentials of both protoporphyrins on VEGF synthesis were very similar. In contrast, analysis of iNOS activity revealed that results obtained with different HO-1 inhibitors are discrepant. Generation of nitric oxide by iNOS was significantly increased by SnPPIX but strongly decreased by ZnPPIX. Similar differences were observed when cell viability was compared. SnPPIX improved the cell survival rate, whereas the same doses of ZnPPIX exerted some cytotoxic effects. In summary, SnPPIX and ZnPPIX can be used as HO-1 inhibitors in some experimental models. However, these compounds produce also HO-independent effects, which can make the interpretation of experiments very uncertain. Thus the involvement of the HO-1 pathway should be always confirmed by more specific methods.

Abstract Specialists in international finance have long been impressed by the fragility of currency pegs. Yet the National Bank of Denmark has been able to maintain the krone’s peg to the euro since the euro came into existence in 1999, and the krone’s peg to the Deutschmark and SDR for 17 years before that. This paper considers a series of hypotheses that may help to account for the exceptional nature of this case. None of these explanations is entirely satisfactory, but collectively they go some way toward explaining the Danish exception.

Hypertension is defined as resistant to treatment when a therapeutic plan including ≥3 hypertension medications failed to sufficiently lower systolic (SBP) and diastolic (DBP) blood pressures (BPs). Most individuals, including those under hypertension therapy, show a "white-coat" effect that could cause an overestimation of their real BP. The prevalence and clinical characteristics of "white-coat" or isolated-office resistant hypertension (RH) has always been evaluated by comparing clinic BP values with either daytime home BP measurements or the awake BP mean obtained from ambulatory monitoring (ABPM), therefore including patients with either normal or elevated asleep BP mean. Here, we investigated the impact of including asleep BP mean as a requirement for the definition of hypertension on the prevalence, clinical characteristics, and estimated cardiovascular (CVD) risk of isolated-office RH. This cross-sectional study evaluated 3042 patients treated with ≥3 hypertension medications and evaluated by 48-h ABPM (1707 men/1335 women), 64.2 ± 11.6 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 522 (17.2%) had true isolated-office RH (elevated clinic BP and controlled awake and asleep ambulatory BPs while treated with 3 hypertension medications), 260 (8.6%) had false isolated-office RH (elevated clinic BP, controlled awake SBP/DBP means, but elevated asleep SBP or DBP mean while treated with 3 hypertension medications), and the remaining 2260 (74.3%) had true RH (elevated awake or asleep SBP/DBP means while treated with 3 medications, or any patient treated with ≥4 medications). Patients with false, relative to those with true, isolated-office RH had higher prevalence of microalbuminuria and chronic kidney disease (CKD), significantly higher albumin/creatinine ratio (p < .001), significantly higher 48-h SBP/DBP means by 9.6/5.3 mm Hg (p < .001), significantly lower sleep-time relative SBP and DBP decline (p < .001), and significantly greater prevalence of a non-dipper BP profile (96.9% vs. 38.9%; p < .001). Additionally, the prevalence of the riser BP pattern, which is associated with highest CVD risk, was much greater, 40.4% vs. 5.0% (p < .001), among patients with false isolated-office RH. The estimated hazard ratio of CVD events, using a fully adjusted model including the significant confounding variables of sex, age, diabetes, chronic kidney disease, asleep SBP mean, and sleep-time relative SBP decline, was significantly greater for patients with false compared with those with true isolated-office RH (2.13 [95% confidence interval: 1.95-2.32]; p < .001). Patients with false isolated-office hypertension and true RH, however, were equivalent for the prevalence of obstructive sleep apnea, metabolic syndrome, obesity, diabetes, microalbuminuria, and chronic kidney disease, and they had an equivalent estimated hazard ratio of CVD events (1.04 [95% confidence interval: .97-1.12]; p = .265). Our findings document a significantly elevated prevalence of a blunted nighttime BP decline in patients here categorized as either false isolated-office RH and true RH, jointly accounting for 82.8% of the studied sample. Previous reports of much lower prevalence of true RH plus a nonsignificant increased CVD risk of this condition compared with isolated-office RH are misleading by disregarding asleep BP mean for classification. Our results further indicate that classification of RH patients into categories of isolated-office RH, masked RH, and true RH cannot be based on the comparison of clinic BP with either daytime home BP measurements or awake BP mean from ABPM, as so far customary in the available literature, totally disregarding the highly significant prognostic value of nighttime BP. Accordingly, ABPM should be regarded as a clinical requirement for proper diagnosis of true RH.

There is strong association between diabetes and increased risk of end-organ damage, stroke, and cardiovascular disease (CVD) morbidity and mortality. Non-dipping (<10% decline in the asleep relative to awake blood pressure [BP] mean), as determined by ambulatory BP monitoring (ABPM), is frequent in diabetes and consistently associated with increased CVD risk. The reported prevalence of non-dipping in diabetes is highly variable, probably due to differences in the study groups (normotensive subjects, untreated hypertensives, treated hypertensives), relatively small sample sizes, reliance only on a single, low-reproducibility, 24-h ABPM evaluation per participant, and definition of daytime and nighttime periods by arbitrary selected fixed clock-hour spans. Accordingly, we evaluated the influence of diabetes on the circadian BP pattern by 48-h ABPM (rather than for 24 h to increase reproducibility of results) during which participants maintained a diary listing times of going to bed at night and awakening in the morning. This cross-sectional study involved 12 765 hypertensive patients (6797 men/5968 women), 58.1 ± 14.1 (mean ± SD) yrs of age, enrolled in the Hygia Project, designed to evaluate prospectively CVD risk by ABPM in primary care centers of northwest Spain. Among the participants, 2954 (1799 men/1155 women) had type 2 diabetes. At the time of study, 525/3314 patients with/without diabetes were untreated for hypertension, and the remaining 2429/6497 patients with/without diabetes were treated. Hypertension was defined as awake systolic (SBP)/diastolic (DBP) BP mean ≥135/85 mm Hg, or asleep SBP/DBP mean ≥120/70 mm Hg, or BP-lowering treatment. Hypertensive patients with than without diabetes were more likely to be men and of older age, have diagnoses of microalbuminuria, proteinuria, chronic kidney disease, obstructive sleep apnea, metabolic syndrome, and/or obesity, plus higher glucose, creatinine, uric acid, and triglycerides, but lower cholesterol and estimated glomerular filtration rate. In patients with diabetes, ambulatory SBP was significantly elevated (p < .001), mainly during the hours of nighttime sleep and initial hours after morning awakening, independent of presence/absence of BP-lowering treatment. Ambulatory DBP, however, was significantly higher (p < .001) in patients without diabetes, mainly during the daytime. Differing trends for SBP and DBP between groups resulted in large differences in ambulatory pulse pressure (PP), it being significantly greater (p < .001) throughout the entire 24 h in patients with diabetes, even after correcting for age. Prevalence of non-dipping was significantly higher in patients with than without diabetes (62.1% vs. 45.9%; p < .001). Largest difference between groups was in the prevalence of the riser BP pattern, i.e., asleep SBP mean greater than awake SBP mean (19.9% vs. 8.1% in patients with and without diabetes, respectively; p < .001). Elevated asleep SBP mean was the major basis for the diagnosis of hypertension and/or inadequate BP control among patients with diabetes; thus, among the uncontrolled hypertensive patients with diabetes, 89.2% had nocturnal hypertension. Our findings document significantly elevated prevalence of a blunted nocturnal BP decline in hypertensive patients with diabetes. Most important, prevalence of the riser BP pattern, associated with highest CVD risk among all possible BP patterns, was more than twice as prevalent in diabetes. Patients with diabetes also presented significantly elevated ambulatory PP, reflecting increased arterial stiffness and enhanced CVD risk. These collective findings indicate that diabetes should be included among the clinical conditions for which ABPM is recommended for proper CVD risk assessment.

Independent prospective studies have found that ambulatory blood pressure (BP) monitoring (ABPM) is more closely correlated with target organ damage and cardiovascular disease (CVD) risk than clinic BP measurement. This is based on studies in which BP was sampled every 15-30 min for ≤24 h, without taking into account that reproducibility of any estimated parameter from a time series to be potentially used for CVD risk assessment might depend more on monitoring duration than on sampling rate. Herein, we evaluated the influence of duration (48 vs. 24 h) and sampling rate of BP measurements (form every 20-30 min up to every 2 h) on the prognostic value of ABPM-derived parameters. We prospectively studied 3344 subjects (1718 men/1626 women), 52.6 ± 14.5 yrs of age, during a median follow-up of 5.6 yrs. Those with hypertension at baseline were randomized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime. At baseline, BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h, and physical activity was simultaneously monitored every min by wrist actigraphy to accurately derive the awake and asleep BP means. Identical assessment was scheduled annually and more frequently (quarterly) if treatment adjustment was required. ABPM profiles were modified to generate time series of identical 48-h duration but with data sampled at 1- or 2-h intervals, or shorter, i.e., first 24 h, time series with data sampled at the original rate (daytime 20-min intervals/nighttime 30-min intervals). Bland-Altman plots indicated that the range of individual differences in the estimated awake and asleep systolic (SBP) and diastolic BP (DBP) means between the original and modified ABPM profiles was up to 3-fold smaller for data sampled every 1 h for 48 h than for data sampled every 20-30 min for the first 24 h. Reduction of ABPM duration to just 24 h resulted in error of the estimated asleep SBP mean, the most significant prognostic marker of CVD events, in the range of -21.4 to +23.9 mm Hg. Cox proportional-hazard analyses adjusted for sex, age, diabetes, anemia, and chronic kidney disease revealed comparable hazard ratios (HRs) for mean BP values and sleep-time relative BP decline derived from the original complete 48-h ABPM profiles and those modified to simulate a sampling rate of one BP measurement every 1 or 2 h. The HRs, however, were markedly overestimated for SBP and underestimated for DBP when the duration of ABPM was reduced from 48 to only 24 h. This study on subjects evaluated prospectively by 48-h ABPM documents that reproducibility in the estimates of prognostic ABPM-derived parameters depends markedly on duration of monitoring, and only to a lesser extent on sampling rate. The HR of CVD events associated with increased ambulatory BP is poorly estimated by relying on 24-h ABPM, indicating ABPM for only 24 h may be insufficient for proper diagnosis of hypertension, identification of dipping status, evaluation of treatment efficacy, and, most important, CVD risk stratification.