Increase in Carotid Intima-Media Thickness in Grade I Hypertensive Subjects

We studied 74 never-treated grade I hypertensive subjects aged 18 to 45 years and 20 normotensive control subjects to define the rate of increase in carotid intima-media thickness (IMT) and the potential role played by the various risk factors. IMT was assessed as mean IMT and as maximum IMT in the right and left common carotid artery, carotid bulb, and internal carotid artery at baseline and at the 5-year follow-up. In grade I hypertensive subjects, both mean IMT and mean of maximum IMT were significantly higher compared with baseline values. Compared with normotensive subjects, both mean IMT and maximum IMT increased significantly (at least P <0.01) in each carotid artery segment. The increase in cumulative IMT was 3.4-fold for mean IMT and 3.2-fold for mean of maximum IMT. Levels of mean arterial pressure at 24-hour monitoring and total serum cholesterol were factors potentially linked to the increment in mean IMT and mean of maximum IMT. Age was also relevant for the increment in mean of maximum IMT, whereas body mass index played some role in the increment of mean IMT. During the follow-up, mean IMT and mean of maximum IMT increased to a greater degree in white-coat hypertensive subjects (n=35) and sustained hypertensive subjects (n=39) than in normotensive control subjects. No differences were found between white-coat hypertensive subjects and sustained hypertensive subjects for both mean IMT and maximum IMT. Levels of mean arterial pressure at 24-hour monitoring affected the increment in IMT in both white-coat hypertensive subjects and sustained hypertensive subjects. In conclusion, our findings indicate that carotid IMT is greater and grows faster in white-coat hypertensive subjects than in normotensive subjects without significant differences with sustained hypertensive patients

Central blood pressure is an independent predictor of future hypertension in young to middle-aged stage 1 hypertensives.

The aim of the present study was to evaluate the association of central blood pressure (BP) with organ damage and risk of future hypertension in a cohort of young to middle-aged patients.We studied 305 subjects screened for stage 1 hypertension to determine which subjects developed hypertension needing therapy according to current guidelines. Central BP was obtained from radial artery tonometry. Organ damage was the presence of left ventricular hypertrophy and/or microalbuminuria.In a multiple logistic regression including ambulatory 24-h BP, central mean BP was associated with presence of end-organ damage (p = 0.003). In the subjects divided according to whether their central mean BP was above or below the median, subjects with high central mean BP presented an earlier impairment of arterial distensibility and developed sustained hypertension more frequently compared with those with low central mean BP (p0.001). In logistic analyses, central mean BP was an independent predictor of future hypertension (p0.001) and remained associated with outcome when 24-h BP was included in the same model (p = 0.006).In young to middle-aged subjects in the early stage of hypertension, central mean BP is a useful adjunct to brachial BPs to better define the individual risk profile

Predictive value of night-time heart rate for cardiovascular events in hypertension. The ABP-International study

Background - Data from prospective cohort studies regarding the association between ambulatory heart rate (HR) and cardiovascular events (CVE) are conflicting. Methods - To investigate whether ambulatory HR predicts CVE in hypertension, we performed 24-hour ambulatory blood pressure and HR monitoring in 7600 hypertensive patients aged 52 ± 16 years from Italy, U.S.A., Japan, and Australia, included in the ‘ABP-International’ registry. All were untreated at baseline examination. Standardized hazard ratios for ambulatory HRs were computed, stratifying for cohort, and adjusting for age, gender, blood pressure, smoking, diabetes, serum total cholesterol and serum creatinine. Results - During a median follow-up of 5.0 years there were 639 fatal and nonfatal CVE. In a multivariable Cox model, night-time HR predicted fatal combined with nonfatal CVE more closely than 24 h HR (p = 0.007 and = 0.03, respectively). Daytime HR and the night:day HR ratio were not associated with CVE (p = 0.07 and = 0.18, respectively). The hazard ratio of the fatal combined with nonfatal CVE for a 10-beats/min increment of the night-time HR was 1.13 (95% CI, 1.04–1.22). This relationship remained significant when subjects taking beta-blockers during the follow-up (hazard ratio, 1.15; 95% CI, 1.05–1.25) or subjects who had an event within 5 years after enrollment (hazard ratio, 1.23; 95% CI, 1.05–1.45) were excluded from analysis. Conclusions - At variance with previous data obtained from general populations, ambulatory HR added to the risk stratification for fatal combined with nonfatal CVE in the hypertensive patients from the ABP-International study. Night-time HR was a better predictor of CVE than daytime HR

Cognitive Functions and Cognitive Reserve in Relation to Blood Pressure Components in a Population-Based Cohort Aged 53 to 94 Years

In 288 men and women from general population in a cross-sectional survey, all neuropsychological tests were negatively associated with age; memory and executive function were also positively related with education. The hypertensives (HT) were less efficient than the normotensives (NT) in the test of memory with interference at 10 sec (MI-10) (−33%, P = 0.03), clock drawing test (CLOX) (−28%, P < 0.01), and mini-mental state examination (MMSE) (−6%, P = 0.02). Lower MMSE, MI-10, and CLOX were predicted by higher systolic (odds ratio, OR, 0.97, P = 0.02; OR 0.98, P < 0.005; OR 0.95, P < 0.001) and higher pulse blood pressure (BP) (OR 0.97, P = 0.02; OR 0.97, P < 0.01; and 0.95, P < 0.0001). The cognitive reserve index (CRI) was 6% lower in the HT (P = 0.03) and was predicted by higher pulse BP (OR 0.82, P < 0.001). The BP vectors of lower MMSE, MI-10, and CLOX were directed towards higher values of systolic and diastolic BP, that of low CRI towards higher systolic and lower diastolic. The label of hypertension and higher values of systolic or pulse BP are associated to worse memory and executive functions. Higher diastolic BP, although insufficient to impair cognition, strengthens this association. CRI is predicted by higher systolic BP associated to lower diastolic BP

Arterial stiffness, central hemodynamics, and cardiovascular risk in hypertension

This review summarizes several scientific contributions at the recent Satellite Symposium of the European Society of Hypertension, held in Milan, Italy. Arterial stiffening and its hemodynamic consequences can be easily and reliably measured using a range of noninvasive techniques. However, like blood pressure (BP) measurements, arterial stiffness should be measured carefully under standardized patient conditions. Carotid-femoral pulse wave velocity has been proposed as the gold standard for arterial stiffness measurement and is a well recognized predictor of adverse cardiovascular outcome. Systolic BP and pulse pressure in the ascending aorta may be lower than pressures measured in the upper limb, especially in young individuals. A number of studies suggest closer correlation of end-organ damage with central BP than with peripheral BP, and central BP may provide additional prognostic information regarding cardiovascular risk. Moreover, BP-lowering drugs can have differential effects on central aortic pressures and hemodynamics compared with brachial BP. This may explain the greater beneficial effect provided by newer antihypertensive drugs beyond peripheral BP reduction. Although many methodological problems still hinder the wide clinical application of parameters of arterial stiffness, these will likely contribute to cardiovascular assessment and management in future clinical practice. Each of the abovementioned parameters reflects a different characteristic of the atherosclerotic process, involving functional and/or morphological changes in the vessel wall. Therefore, acquiring simultaneous measurements of different parameters of vascular function and structure could theoretically enhance the power to improve risk stratification. Continuous technological effort is necessary to refine our methods of investigation in order to detect early arterial abnormalities. Arterial stiffness and its consequences represent the great challenge of the twenty-first century for affluent countries, and “de-stiffening” will be the goal of the next decades

orthostatic hypotension does not increase cardiovascular risk in the elderly at a population level

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Circular RNAs Could Encode Unique Proteins and Affect Cancer Pathways

CircRNAs constitute a novel class of RNA, generally considered as non-coding RNAs; nonetheless, their coding potential has been under scrutiny. In this work, we systematically explored the predicted proteins of more than 160,000 circRNAs detected by exome capture RNA-sequencing and collected in the MiOncoCirc pan-cancer compendium, including normal and cancer samples from different types of tissues. For the functional evaluation, we compared their primary structure and domain composition with those derived from the same linear mRNAs. Among the 4362 circRNAs potentially encoding proteins with a unique primary structure and 1179 encoding proteins with a novel domain composition, 183 were differentially expressed in cancer. In particular, eight were associated with prognosis in acute myeloid leukemia. The functional classification of the dysregulated circRNA-encoded polypeptides showed an enrichment in the heme and cancer signaling, DNA-binding, and phosphorylation processes, and disclosed the roles of some circRNA-based effectors in cancer

The 2023 hypertension guidelines of the European Society of Hypertension: a commentary

The 2023 hypertension guidelines of the European Society of Hypertension (ESH) have been published in the December issue of the official Journal of the Society (Journal of Hypertension),1 where they are freely available online. Compared to the guidelines published 5 years ago,2 the new guidelines address issues never or only marginally addressed before, including a large number of comorbidities to hypertension that may change the approach to antihypertensive management. [...

Ambulatory Monitoring Uncorrected for Placebo Overestimates Long-term Antihypertensive Action

Abstract &apos;This study compares blood pressure (BP) changes during active antihypertensive treatment and placebo as assessed by conventional and anlbulatory BP measurement. Older patients (260 years, n=337) with isolated systolic hypertension by conventional sphygrnomanometry at the clinic were rando~nized to placebo or active treatment consisting of nitrendipine (10 to 40 mgid), with the possil~le addition oF enalapril (5 10 20 mgid) ;~nd/or hydrochlorothiazide (12.5 Lo 25 mg/d). At baseline, clinic systolic/diastolic BP averaged 175186 mm Hg and 24-hour and daytimc ;~mbulatory BPs averaged 148180 and 154185 mm Hg, respectively. After 13 months (median) of active treatment, clinic BP had dropped by 22.717.0 mm Hg and 24-hour and daytime BPs by 10.514.5 and 9.714.3 mm Hg, respectively (P&lt;.001 for all). However, clinic (9.811.6 mm Hg), 24-hour (2.11 1.1 nini Hg), and daytime (2.911.0 mm Hg) BPs decreased also during placebo (P&lt;.05, except for daytime diastolic BP); these decreases represented 43%/23%, 20%/24%, and 30%/23% of the corresponding BP fall during active treatment. After subtraction of placebo effects, the net BP reductions during active treatment averaged only 12. 915.4, 8.313.4, and 6.813.2 mm Hg for clinic, 24-hour, and daytime BPs, respectively. The effect of active treatment was also subject to diurnal variation (R.05). Changes during placebo in hourly systolic and diastolic BP means amounled to (median) 21% (range, -1% to 42%) and 25% (-3% to 72%), respectively, of the corresponding changes during active treatment. In conclusion, expressed in millimeters of mercury, the effect of antihypertensive treatment on BP is larger with conventional than with ambulatory measurement. Regardless of whether BP is measured by conventional sphygmomanometry or ambulatory monitoring, a substantial proportion of the long-tern~ BP changes observed during active treatrnent may be attributed to placebo effects. Thus, ambulatory monitoring uncorrected for placebo or control observations, like conventional sphygmomanometry, overestimates BP responses in clinical trials of long duration. (Hypertension. lYY6;27[part 1]:414-420.) Key IYords blood pressure monitoring, ambulatory antihypertensive therapy clinical trials blood pressure monitoring placebo T he SYST-EUR Trial is a double-blind, placebocontrolled outcome trial in older patients with isolated systolic hypertension that the European Working Party on High Blood Pressure in the Elderly is currently conducting in Western and Eastern Europe and in 1srael.l Presently, the 3000 patients originally planned lor have been randomized. In accordance with current clinical practice,2 only conventional sphygmomanometric BP readings by an auscultating observer determine a patient&apos;s eligibility for randomization and guide the stepwise adjustments of treatment during the double-blind phase of the trial. &apos; In addition to conventional sphygmomanometry, arnbulatory BP monitoring is increasingly used in clinical trials to evaluate the magnitude and duration of the BP-lowering action of antihypertensive agents. SYST-EUR centers can opt to monitor their patients in an attempt to evaluate whether the ambulatory BP, over ancl above the clinic BP, is helplul in predicting cardiovascular events.&apos; This article builds on the data collected so Tar in the SYST-EUR Trial1 and contrasts the effects Received August 25, 1995; first decision September 18, 1995; revision accepted October 31, 1995. Correspondence to Jan A. Staessen, MD, PhD, Klinisch Labo-~;ltol.iuni Ilypertensie, Inwendige Geneeskunde-Cardiologie, U Z Gaslhuisberg, Herestraat 49, Belgiu~n. 0 L996 American Heart Association, Inc. of antihypertensive treatment and placebo as assessed by conventional sphygmomanometry and ambulatory monitoring. 11 extends the findings o l a previous article that was limited to the placebo arm of the triaL4 Methods Study Design &apos;The protocol of the SYST-EUR Trial has been published elsewhere.&apos; It was approved by the Ethics Committee of the Faculty of Medicine at the University of Leuven as well as by the institutional review committees of all participating centers. Patients were eligible (I) if they were at least 60 years old; (2) if, on a placebo during the run-in phase, their sitting SBP ranged from 160 to 219 mm Hg with a DBP below 95 mm Hg; (3) if their standing SBP was 140 mm Hg or higher; and (4) if, after having been informed, they voluntarily consented to be enrolled. The BP criteria for entry rested on the averages of six silting and six standing readings, ie, two in each position at three baseline visits I month apart. Eligil~le patients were stratifed by sex and the presence versus absence of cardiovascular complications and were randomized to double-blind treatment with active medication or placebo. Aclive treatment consisted of nitrendipine BP and Other Measurements SYST-EUR centers opting to take part in ambulatory rnonitoring were asked to perform recordings at baseline, at 6 and 12 months, and annually thereafter? Validated5.Wonitors were programmed to obtain measurements at intervals not greater than 30 minutes. The conventional BP corresponding to each ambulatory recording was the average of the two readings with patients in the sitting position obtained at the nearest clinic visit. The patients were interviewed at baseline and follow-up concerliing their smoking habits, habitual alcohol intake, and activities of daily l i~i n g .~,~ In addition, the serum activity of yglulanlyllranspeptidase was determined as an index of alcohol intake.&quot; Analysis of the Diurnal BP Profile If the ambulatory recordings were longer than 24 hours, only the first 24 hours was used for analysis. Recordiligs were excluded whenever the available readings constituted less than 80% of those program~netl or covered less than 22 consecutive hours. I&apos;he editing criterial&quot;.ll considered for tlelelion of readings from the recordings were (1) SBP&lt;DBP, (2) SBP &gt;240 or &lt;40 mm Hg, (3) DBP &gt;I40 or &lt;40 mm Hg, (4) pulse rate &gt;l50 or &lt;40 beats per minute, and (5) pulse pressure &lt;10% of SBP. The 24-hour, daytime, and nighltime pressures and hourly BP means were weighted for the time between consecutive readings. l 2 Daytime was from I0 AM to 8 PM and nighttime from mitlnight to 6 AM. These dcfnitions of daytime ancl nighttime have been used in previous s t~d i e s~~&apos;~~~ and exclude the transition periods in the morning and evening during which BP changes rapidly. The awake and sleeping periods were determined from diary cards kept by the patients on recording days.7 Statistical Analysis Database management and statistical analyses were performed with the SAS software (SAS Institute Inc). Statistical methods included Student&apos;s t test and linear regression analysis. Diurnal BP profiles, drawn from hourly BP means, were contrasted by repeated measures ANOVA,I4 considering as main effects treatment allocation (active versus placebo) and time of day. For establishment of whether the antihypertensive action was steady over 24 hours, the model also tested for a treatment-time interaction. The net treatment effect, sometimes referred to as the double delta of BP,&quot; was calculated by subtracting the mean change from baseline during placebo from the corresponding change during active treatment. The 95% confidence limits about the net treatment effect showed the times during the day when the BP reduction was significant. The reproducibility of duplicate measurements was studied by the Bland and Altman technique.lh For co~nparison of the reproducibility of various BP measurements, the repeatability coefficients were expressed as a percentage of nearly maximal variation, ie. the interval encompassing four times the S D of the averaged tluplicate measurements. Results Data Available for Analysis On May 15, 1995, 407 patients had their ambulatory BP recorded during the run-in phase of the trial and at least once after randomization. In 174 of these patients, duplicate recordings had been obtained at baseline. After patients with incomplete recordings were excluded, these numbers were 337 and 118, respectively. The 792 ambulatory recordings included in the present analysis comprised a total of 51 960 single BP readings, of which only 1.5% complied with at least one of the criteria considered for editing. In 501 recordings (63%), no single reading met the editing criteria. Because editing did not influence the results, only analyses based on unedited recordings are presented. Patient Characteristics at Randomization The patients allocated to placebo (n=169) and active treatment (n= 168) had the same characteristics at randomization. They comprised 142 men and 195 women. Cardiovascular complications were present in 94 patients. Of the 337 patients, 167 had been treated during the 6 months before they were considered for entry into the trial, 30 with diuretics, 19 with P-blockers, 21 with converting enzyme inhibitors, 33 with calcium entry blockers, and 64 with various other drugs or with a combination of several antihypertensive agents. Previous antihypertensive treatment was usually discontinued l month before the first run-in visit during placebo. The median time interval between the latter visit and randomization was 76 days (range, 36 to 300) in the previously treated patients and 70 days (range, 20 to 300) in the other patients. In all 337 patients, age averaged 7026 (5SD) years (range, 60 to 100). Body mass index was 26.153.3 kg/m2 in men and 26.554.0 kg/m2 in women. SBP at the clinic averaged 175k 12 mm Hg (range, 160 to 217) and DBP 8656 mm Hg (range, 49 to 94). The corresponding 24-hour pressures were 1485 16 mm Hg (range, 1 10 to 202) and 8059 lnln Hg (range, 58 to 138), respectively. Daytime versus awake and nighttime versus sleeping SBP and DBP did no1 differ Reproducibility of Clinic and Ambulatory Pressures at Baseline In 118 patients, ambulatory monitoring had been repeated during the run-in phase of the trial at a median interval of 33 days (range, 7 to 127). Reproducibility of the clinic pressure was studied by contrasting the averages of the two readings obtained with patients in the sitting position at two outpatient visits. Group means of the clinic and ambulatory pressures could be reproduced without significant changes in their values, except for the 24-hour, daytime, and awake SBP, which decreased (1-&apos;&lt;.05) by approximately 2 mm Hg, and for the awake DBP, which decreased (Pc.05) by 1 mm Hg Treatment Effects on Clinic and Ambulatory Pressures Follow-up averaged 13 months (median) (range, 4 to 30). Of the 337 paticnts, 310 remained on the lirst-line medication, ie, nitrendipine (n=151; daily dose, 27212 mg) or matching placebo (n=159). At the follow-up visit. second-and third-line medications had been started in 49 (1427 mg) and 21 (2226 mg) patients on active treatment and in 84 and 47 patients on placebo. Active treatment decreased the clinic and ambulatory SBP and DBP, but also during placebo these pressures tended to decline Over the follow-up period, no significant changes occurred in the patients&apos; body weight (mean change?SD, -0.123.4 kg), smoking habits (-0.625.3 g tobacco per day), alcohol intake (-0.625.3 gld), serum y-glutamyltranspeptidase activity ([email protected]%), and score for the activities of daily living (median change, 0; range, -5 to +I). Modifications over the follow-up period in these lifestyle measures and previous antihypertensive treatment were not correlated with the decrease in the ambulatory BP values in the placebo group. The changes in body weight constituted the only possible exception because they tended to be positively associated with the changes in the 24-hour DBP (regression coefficientkSE, 0.2920.16 mm tiglkg; P=.07) and in the daytime (0.3820.20 mm Hgl kg, P=.OS) and nighttime (0.3520.19 mm Hglkg, P=.07) DBPs. Treatment Effects on Diurnal BP Profiles At both baseline and follow-up, time of day was a significant (P&lt;.001) source of BP variation. At baseline, treatment allocation (!&apos;=.g6 for SBP, P=.39 for DBP) as well as the interaction terms between treatment and time of day were not significant (P=.75 and .40, respectively). These results confirmed that during the run-in phase, the diurnal BP profiles were superimposable in the two treatment arms of the trial At follow-up, active treatment shifted (P&lt;.001) the diurnal BP profile downward Disparity Between Clinic and Ambulatory Measurements At baseline, the correlation coefficients between the clinic and daytime measurements were .46 for SBP and .39 for DBP. The corresponding correlation coefficients at fc&gt;llow-up were .57 and .49 in the placebo group and .32 and .35 during active treatment (PC.001 for all correlations). Clinic SBP was on all occasions higher (P&lt;.001) than daytime SBP, ie, 21215 mm Hg at baseline, 14k17 mm Hg during placebo at follow-up, and 9&amp;19 mm Hg during active treatment. In contrast, the mean differences between the clinic and daytime DBPs were small, averaging l + 10 mm Hg at baseline as well as during placebo at follow-up and -2+ 11 mm Hg during active treatment. 1)iscussion After approximately 1 year, the net separation in the clinic pressure between the two treatment groups aver- Approximately one third of the patients enrolled in the SYST-EUR Trial undergo ambulatory monitoring, in addition to conventional sphygmomanometry. The net separation between the two treatment arms after a median follow-up of approximately 1 year was considerably smaller for the ambulatory than for the clinic pressures, ie, 4.912.0 mm Hg less for the 24-hour pressures and 6.112.2 mm Hg less for the daytime pressures. Thus, the differentiation in the clinic pressures between the two treatment groups was 55%/59% larger than observed for the 24-hour pressures and 90%/69% larger than for the daytime pressures. The currently prevails that ambulatory recordings more closely reflect a patient&apos;s habitual BP level than the few readings taken by an auscultating observer in the stressful hospital e n v i r~n m e n t .~~-~T h e present study therefore suggests that the true BP responses in a long-term randomized clinical trial are overestimated by conventional sphygmomanometry by as much as 50% to 90%. The latter estimate is in agreement with a large meta-analysis of prospective observational studies in the field of hypertension.24 A correction for regression dilution bias was calculated by introducing the so-called usual BP, defined as an individual&apos;s average BP over several years. According to these ~alculations,2~ a 12 mm Hg difference in the baseline pressure was rescaled into a 7.5 mm Hg contrast in the usual pressure. Thus, BP measurements at a single occasion (baseline) were felt to inflate the gradient in the usual pressure by approximately 60%. Staessen et a1 Ambulatoly BP Monitoring During Placebo 417 BP measurements by conventional sphygmomanometry have guided patient recruitment and therapy in most clinical trials in the field of hypertension, including all outcome trials.2Wespite their track record, conventional BP readings are subject to the so-called placebo effect, often attributed to a gradual weakening of the alerting reaction22,23 and to a regression-to-the-mean phenomenon.2&quot;-29 If conventional and anlbulatory measurements are repeated within the same subjects, the latter are characterized by greater reprodu~ibility,2~~ attributable to the absence-of digit preferen~e,&quot;~ ob- server bias,&quot;) and the white coat reaction22,2&apos;.31 but foremost to the greater number of readings averaged for calculation of the ambulatorv v a l~e s . 3~ This was confirmed in the present study, in which the clinic pressures dui-ing the placebo run-in period showed higher repeatahilily cc~cficicnts, signirying lowcr intrainclividual reproducibility, than the 24-hour and daytime pressures. Debate continues over whether ambulatory BP measurements decrease during placebo. The intra-arterially measured an~bulatory pressure has been demonstrated to remain at the same level when hypertensive patients were put on a placebo for 6 weeks.&quot;klong simiiar lines, in a 6-week study with a noninvasive recording technique,&apos;4 the ambulatory pressure fell only slightly during the initial recording hours, such that the average BP over 24 hours stayed unaffected. On balance, most publications currently favor the view that the ambulatory pressure is not subject to a placebo e f f e~t . &apos; &quot; &apos; &quot;~~-~~. -7 &quot; -~~ HOWever, few long-term studies on this subject have been published. A previous SYST-EUR publication4 based on 112 patients and limited to the placebo arm of the trial showed that after a median follow-up of 1 year the clinic SUP fell by 6.6 mm tIg (P&lt;.001) and the 24-hour and daytime SBPs by 2.4 (P&lt;.05) and 2.6 mm Hg (P=.06), respectively. The corresponding decreases in DBP were smaller, averaging only 1.4 (P-.06), 1.1, and 0.7 mm Hg.4 These estimates were of the same order of magnitude as in the present analysis, in which, because of the larger number of patients, the changes during placebo in the clinic and 24-hour DBPs also reached a level of statistical significance. The decline in the ambulatory BP values, amounting to approximately 2 mm Hg, may seem trivial and negligible. However, in relative terms they represented 43%1 23%, 20%/24%, and 30%/23% of the corresponding reductions in the clinic, 24-hour, and daytime SBPs/DBPs during active treatment. As far as the clinic pressure is vations, eg, during placebo, cannot be refuted and is part of the established culture among trialists. If this rule is true for the clinic pressure, then in opposition to the prevailing view in the literat~re,~3.1&quot;2&quot;-29,&quot;3-4&quot;t also needs to be applied for the ambulatory pressure, of which a substantial fraction may be explained by placebo-like effects. This reasoning not only involves the average 24-hour and daytime pressures but also the hourly BP means, which represent the treatment effects through the whole day. In the present study, the decreases in the hourly BP values during placebo constituted up to 70% of what was observed during active treatment. In the present study, the reduction in the clinic SBP during placebo may have been influenced by the 160 mm Hg threshold used to select the patients and by a subsequent regression-to-the-mean phenomenon. However, other mechanisms are also likely to have been at play because decreases during placebo were observed in the clinic DBP, which in all patients was lower than 95 mm Hg, as well as in the ambulatory measurements, which were not used to select the patients. Familiarization with the hospital environment or the procedure of ambulatory monitoring could be examples of such mechanisms. In addition, the present analysis demonstrated that changes in lifestyle were unlikely to be involved to a major extent. The clinic SBP was 21 mm Hg higher than the daytime pressure at baseline but only 14 and 9 mm Hg higher at follow-up during placebo and active treatment, respectively. These findings suggest that the white coat effect wears off as time goes by. It may also be attenuated by antihypertensive treatment, which probably dampens the BP surges caused by sympathetic arousal to the Staesserz et a1 Ambulatory BP Monitoring During Placebo 419 observer measuring the BP. Furthermore, the decreases in the ambulatory measurements during placebo and active treatlncnt were proportional to the BP level a1 baseline. T h e regression equations derived in the present studv vredicted that the 24-hour SBP would decrease , . by only 3.0 mm H g during active treatment in patients whose 24-hour SBP at entry was 135 mm Hg, ie, the 95th percentile in normotensive s~b j e c t s .~~h~s , in agreement with a previous report,47 prescribing antihypertensive medications to patients with a high clinic but low ambulatory pressure would not result in a substantial reduction of the habitual BP through the day. T h e issue of whether ambulatory measurements need to be corrected for placebo is not without importance, as it inherently touches o n the design of clinical trials in the field of hypertension. Some experts4x feel that ambulatory monitoring eliminates only observer bias and expectation4&quot; and does not remove regression-to-the-mean and patient-related factors that contribute to the placebo effect. Other researchers defend the point of view that ambulatory monitoring would make control observations during placebo s u p e r f l~o u s .~~ If this were true, trials making use of the new technique could investigate antihypertensive interventions just by comparing the B P levels before and after therapy. T h e present findings suggest that the latter approach may lead t o a n overestimation of the true antihypertensive effect and should therefore be abandoned at least in long-term trials. A correction for placebo may even be warranted in shortterm trials because the reproducibility data in this study showed that after a median interval of 1 month the average 24-hour and daytime SBPs decreased during placebo by 1.8 and 2.4 mm Hg, respectively. Thus, clinical trials relying on ambulatory monitoring should adhere t o the same design standards as those making use of conventional sphygmomanometry. Despite theselimitations, ambulatory monitoring, compared with conventional B P readings, offers the advantage of providing information o n B P control through the whole day and makes it possible t o economize o n sample size in crossover but not parallel group trials.&quot

Serum Uric Acid Predicts All-Cause and Cardiovascular Mortality Independently of Hypertriglyceridemia in Cardiometabolic Patients without Established CV Disease: A Sub-Analysis of the URic acid Right for heArt Health (URRAH) Study

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan-Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (&gt;= 4.7 mg/dL) and CVM (&gt;= 5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12-1.40], p &lt; 0.001) and CVM (1.31 [1.11-1.74], p &lt; 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12-1.43], p &lt; 0.001) and hypertriglyceridemia (1.31 [1.02-1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23-1.73], p &lt; 0.001) and hypertriglyceridemia (HR 1.31 [0.99-1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels