Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial-First progress report.

High blood pressure (BP) and type-2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT-HTM (NCT04299529) is an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55-75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow-up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run-in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro-albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2 mm Hg and 137.1/82.7 mm Hg, respectively, resulting in a prevalence of white-coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low-resource sub-Saharan centers proved the feasibility of this multi-ethnic trial. The COVID-19 pandemic caused delays and differential recruitment rates across centers.

Biomarker-based assessment of collagen cross-linking identifies patients at risk of heart failure more likely to benefit from spironolactone effects on left atrial remodelling. Insights from the HOMAGE clinical trial.

AIMS: The HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C-terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio (CITP:MMP-1), associated with high collagen cross-linking, had less improvement in diastolic function with spironolactone. We evaluated the interaction between serum CITP:MMP-1 and spironolactone on cardiac function in the HOMAGE trial. METHODS AND RESULTS: Patients at risk of HF were randomized to spironolactone (n = 260) or not (n = 255). Blood sampling and echocardiography were done at baseline, one and nine months. CITP:MMP-1 was used as an indirect measure of collagen cross-linking. Higher baseline CITP:MMP-1 (i.e. lower collagen cross-linking) was associated with greater reductions in LAVI with spironolactone at both one (p = 0.003) and nine (p = 0.01) months, but no interaction was observed for E:A ratio. Spironolactone reduced LAVI after one and nine months only for those patients in the third tertile of CITP:MMP-1 (estimated lowest collagen cross-linking) [mean differencesspiro/control : -1.77 (95% confidence interval, CI -2.94 to -0.59) and -2.52 (95% CI -4.46 to -0.58) mL/m2 ; interaction pacross-tertiles  = 0.005; interaction pthird tertile  = 0.008] with a similar trend for N-terminal pro-B-type natriuretic peptide which was consistently reduced by spironolactone only in the lowest collagen cross-linking tertile [mean differencesspiro/control : -0.47 (95% CI -0.66 to -0.28) and -0.31 (95% CI -0.59 to -0.04) ng/L; interaction pacross-tertiles  = 0.09; interaction pthird tertile < 0.001]. CONCLUSIONS: These findings suggest that, for patients at risk of HF, the effects of spironolactone on left atrial remodelling may be more prominent in patients with less collagen cross-linking (indirectly assessed by serum CITP:MMP-1).

Reproducibility of Retinal Microvascular Traits Decoded by the Singapore I Vessel Assessment Software Across the Human Age Range.

BACKGROUND: Retinal microvascular traits predict adverse health outcomes. The Singapore I Vessel Assessment (SIVA) software improved automated postprocessing of retinal photographs. In addition to microvessel caliber, it generates measures of arteriolar and venular geometry. Few studies addressed the reproducibility of SIVA measurements across a wide age range. METHODS: In the current study, 2 blinded graders read images obtained by nonmydriatic retinal photography twice in 20 11-year-old children, born prematurely (n = 10) or at term (n = 10) and in 60 adults (age range, 18.9-86.1 years). RESULTS: Former preterm compared with term children had lower microvessel diameter and disorganized vessel geometry with no differences in intraobserver and interobserver variability. Among adults, microvessel caliber decreased with age and blood pressure and arteriolar geometry was inversely correlated with female sex and age. Intraobserver differences estimated by the Bland-Altman method did not reach significance for any measurement. Across measurements, median reproducibility (RM) expressed as percent of the average trait value was 8.8% in children (median intraclass correlation coefficient [ICC], 0.94) and 8.0% (0.97) in adults. Likewise, interobserver differences did not reach significance with RM (ICC) of 10.6% (0.85) in children and 10.4% (0.93) in adults. Reproducibility was best for microvessel caliber (intraobserver/interobserver RM, 4.7%/6.0%; ICC, 0.98/0.96), worst for venular geometry (17.0%/18.8%; 0.93/0.84), and intermediate for arteriolar geometry (10.9%/14.9%; 0.95/0.86). CONCLUSIONS: SIVA produces repeatable measures of the retinal microvasculature in former preterm and term children and in adults, thereby proving its usability from childhood to old age.

Prevalence, Treatment, and Control Rates of Conventional and Ambulatory Hypertension Across 10 Populations in 3 Continents.

Hypertension is a major global health problem, but prevalence rates vary widely among regions. To determine prevalence, treatment, and control rates of hypertension, we measured conventional blood pressure (BP) and 24-hour ambulatory BP in 6546 subjects, aged 40 to 79 years, recruited from 10 community-dwelling cohorts on 3 continents. We determined how between-cohort differences in risk factors and socioeconomic factors influence hypertension rates. The overall prevalence was 49.3% (range between cohorts, 40.0%-86.8%) for conventional hypertension (conventional BP ≥140/90 mm Hg) and 48.7% (35.2%-66.5%) for ambulatory hypertension (ambulatory BP ≥130/80 mm Hg). Treatment and control rates for conventional hypertension were 48.0% (33.5%-74.1%) and 38.6% (10.1%-55.3%) respectively. The corresponding rates for ambulatory hypertension were 48.6% (30.5%-71.9%) and 45.6% (18.6%-64.2%). Among 1677 untreated subjects with conventional hypertension, 35.7% had white coat hypertension (23.5%-56.2%). Masked hypertension (conventional BP <140/90 mm Hg and ambulatory BP ≥130/80 mm Hg) occurred in 16.9% (8.8%-30.5%) of 3320 untreated subjects who were normotensive on conventional measurement. Exclusion of participants with diabetes mellitus, obesity, hypercholesterolemia, or history of cardiovascular complications resulted in a <9% reduction in the conventional and 24-hour ambulatory hypertension rates. Higher social and economic development, measured by the Human Development Index, was associated with lower rates of conventional and ambulatory hypertension. In conclusion, high rates of hypertension in all cohorts examined demonstrate the need for improvements in prevention, treatment, and control. Strategies for the management of hypertension should continue to not only focus on preventable and modifiable risk factors but also consider societal issues.

Renal artery and parenchymal changes after renal denervation: assessment by magnetic resonance angiography.

OBJECTIVES: Relatively little is known about the incidence of long-term renal damage after renal denervation (RDN), a potential new treatment for hypertension. In this study the incidence of renal artery and parenchymal changes, assessed with contrast-enhanced magnetic resonance angiography (MRA) after RDN, is investigated. METHODS: This study is an initiative of ENCOReD, a collaboration of hypertension expert centres. Patients in whom an MRA was performed before and after RDN were included. Scans were evaluated by two independent, blinded radiologists. Primary outcome was the change in renal artery morphology and parenchyma. RESULTS: MRAs from 96 patients were analysed. Before RDN, 41 renal anomalies were observed, of which 29 mostly mild renal artery stenoses. After a median time of 366 days post RDN, MRA showed a new stenosis (25-49% lumen reduction) in two patients and progression of pre-existing lumen reduction in a single patient. No other renal changes were observed and renal function remained stable. CONCLUSIONS: We observed new or progressed renal artery stenosis in three out of 96 patients, after a median time of 12 months post RDN (3.1%). Procedural angiographies showed that ablations were applied near the observed stenosis in only one of the three patients. KEY POINTS: • The incidence of vascular changes 12 months post RDN was 3.1%. • No renal vascular or parenchymal changes other than stenoses were observed. • Ablations were applied near the stenosis in only one of three patients.

Prevalence and Determinants of Masked Hypertension Among Black Nigerians Compared With a Reference Population.

Hitherto, diagnosis of hypertension in sub-Saharan Africa was largely based on conventional office blood pressure (BP). Data on the prevalence of masked hypertension (MH) in this region is scarce. Among individuals with normal office BP (<140/90 mm Hg), we compared the prevalence and determinants of MH diagnosed with self-monitored home blood pressure (≥135/85 mm Hg) among 293 Nigerians with a reference population consisting of 3615 subjects enrolled in the International Database on Home Blood Pressure in Relation to Cardiovascular Outcomes. In the reference population, the prevalence of MH was 14.6% overall and 11.1% and 39.6% in untreated and treated participants, respectively. Among Nigerians, the prevalence standardized to the sex and age distribution of the reference population was similar with rates of 14.4%, 8.6%, and 34.6%, respectively. The mutually adjusted odds ratios of having MH in Nigerians were 2.34 (95% confidence interval, 1.39-3.94) for a 10-year higher age, 1.92 (1.11-3.31) and 1.70 (1.14-2.53) for 10- or 5-mm Hg increments in systolic or diastolic office BP, and 3.05 (1.08-8.55) for being on antihypertensive therapy. The corresponding estimates in the reference population were similar with odds ratios of 1.80 (1.62-2.01), 1.64 (1.45-1.87), 1.13 (1.05-1.22), and 2.84 (2.21-3.64), respectively. In conclusion, MH is as common in Nigerians as in other populations with older age and higher levels of office BP being major risk factors. A significant proportion of true hypertensive subjects therefore remains undetected based on office BP, which is particularly relevant in sub-Saharan Africa, where hypertension is now a major cause of death.

Persistence of Masked Hypertension in Chinese Patients.

BACKGROUND: Masked hypertension (MH) has 10-15% prevalence and carries risk similar to that of sustained hypertension, but its short-term persistence remains uncertain. METHODS: Forty-five patients with MH (mean age 52.2 years; 37.8% women) were enrolled in the placebo arm of a randomized clinical trial of Chinese medicine (NCT02156024) and followed up for 4 weeks. MH was office normotension (<140/90mm Hg) and daytime (8:00-18:00) hypertension (≥135/85mm Hg). RESULTS: At enrolment, office and daytime systolic/diastolic blood pressure (BP) averaged 129.0/80.6mm Hg and 132.9/88.9mm Hg, respectively. Daytime BP thresholds for MH were met in 5 patients (11.1%) for systolic BP, in 25 (55.6%) for diastolic BP and in 15 (33.3%) for both. At follow-up, systolic and diastolic BP had not changed compared with baseline (P ≥ 0.12), except for a 2.1mm Hg decrease in office systolic BP (P = 0.049). MH remained present in 28 patients (62.2%; 95% CI, 48.1-76.3%), whereas 13 (28.9%; 15.7-42.1%) and 4 (8.9%; 0.6-17.2%) converted to normotension (daytime BP <135/85mm Hg) or sustained hypertension (office BP ≥140/90mm Hg), respectively. Substituting daytime by 24-hour BP, using 130/80mm Hg as threshold, produced consistent results. Systolic office BP at baseline independently predicted persistence of MH or progression to sustained hypertension at 4 weeks (odds ratio per 1 - SD increase, 3.49; 95% CI, 1.06-11.2; P = 0.04). CONCLUSIONS: The information that MH persists over 4 weeks in over two-thirds of this sample of patients should inform future clinical trials and guidelines.

Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides.

Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±-0.065; P<0.001) and integrated discrimination improvement (0.058±0.014; P<0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD.

European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring.

Given the increasing use of ambulatory blood pressure monitoring (ABPM) in both clinical practice and hypertension research, a group of scientists, participating in the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability, in year 2013 published a comprehensive position paper dealing with all aspects of the technique, based on the available scientific evidence for ABPM. The present work represents an updated schematic summary of the most important aspects related to the use of ABPM in daily practice, and is aimed at providing recommendations for proper use of this technique in a clinical setting by both specialists and practicing physicians. The present article details the requirements and the methodological issues to be addressed for using ABPM in clinical practice, The clinical indications for ABPM suggested by the available studies, among which white-coat phenomena, masked hypertension, and nocturnal hypertension, are outlined in detail, and the place of home measurement of blood pressure in relation to ABPM is discussed. The role of ABPM in pharmacological, epidemiological, and clinical research is also briefly mentioned. Finally, the implementation of ABPM in practice is considered in relation to the situation of different countries with regard to the reimbursement and the availability of ABPM in primary care practices, hospital clinics, and pharmacies.

European Society of Hypertension position paper on ambulatory blood pressure monitoring.

Ambulatory blood pressure monitoring (ABPM) is being used increasingly in both clinical practice and hypertension research. Although there are many guidelines that emphasize the indications for ABPM, there is no comprehensive guideline dealing with all aspects of the technique. It was agreed at a consensus meeting on ABPM in Milan in 2011 that the 34 attendees should prepare a comprehensive position paper on the scientific evidence for ABPM.This position paper considers the historical background, the advantages and limitations of ABPM, the threshold levels for practice, and the cost-effectiveness of the technique. It examines the need for selecting an appropriate device, the accuracy of devices, the additional information and indices that ABPM devices may provide, and the software requirements.At a practical level, the paper details the requirements for using ABPM in clinical practice, editing considerations, the number of measurements required, and the circumstances, such as obesity and arrhythmias, when particular care needs to be taken when using ABPM.The clinical indications for ABPM, among which white-coat phenomena, masked hypertension, and nocturnal hypertension appear to be prominent, are outlined in detail along with special considerations that apply in certain clinical circumstances, such as childhood, the elderly and pregnancy, and in cardiovascular illness, examples being stroke and chronic renal disease, and the place of home measurement of blood pressure in relation to ABPM is appraised.The role of ABPM in research circumstances, such as pharmacological trials and in the prediction of outcome in epidemiological studies is examined and finally the implementation of ABPM in practice is considered in relation to the issue of reimbursement in different countries, the provision of the technique by primary care practices, hospital clinics and pharmacies, and the growing role of registries of ABPM in many countries.

Cross-sectional and longitudinal assessment of arterial stiffening with age in European and chinese populations.

As arteries become stiffer with aging, reflected waves move faster and augment late systolic pressure. Few studies have described the age-related changes in both peripheral and central systolic blood pressures in populations. We investigated the age dependency of peripheral (pSBP) and central (cSBP) systolic pressure and pressure amplification (i.e., difference between peripheral and central SBP) in randomly selected participants from European and Chinese populations. Data were collected in 1420 Europeans (mean age, 41.7 years) and 2044 (mean age, 45.1 years) Chinese. In cross-sectional analyses of the population samples cSBP consistently increased more with age than pSBP with the age-related increases being greater in women than men. Repeat assessment of pSBP and cSBP in 398 Europeans and 699 Chinese at a median interval approximately 4 years of follow-up confirmed that also within subjects cSBP rose steeper with aging than pSBP. In conclusion, with aging, pSBP approximates to cSBP. This might explain why in older subjects pSBP becomes the main predictor of cardiovascular complications.

Antihypertensive treatment based on blood pressure measurement at home or in the physician's office: a randomized controlled trial.

CONTEXT: Self-measurement of blood pressure is increasingly used in clinical practice, but how it affects the treatment of hypertension requires further study. OBJECTIVE: To compare use of blood pressure (BP) measurements taken in physicians' offices and at home in the treatment of patients with hypertension. DESIGN, SETTING, AND PARTICIPANTS: Blinded randomized controlled trial conducted from March 1997 to April 2002 at 56 primary care practices and 3 hospital-based outpatient clinics in Belgium and 1 specialized hypertension clinic in Dublin, Ireland. Four hundred participants with a diastolic BP (DBP) of 95 mm Hg or more as measured at physicians' offices were enrolled and followed up for 1 year. INTERVENTIONS: Antihypertensive drug treatment was adjusted in a stepwise fashion based on either the self-measured DBP at home (average of 6 measurements per day during 1 week; n = 203) or the average of 3 sitting DBP readings at the physician's office (n = 197). If the DBP guiding treatment was above (>89 mm Hg), at (80-89 mm Hg), or below (<80 mm Hg) target, a physician blinded to randomization intensified antihypertensive treatment, left it unchanged, or reduced it, respectively. MEAN OUTCOME MEASURES: Office and home BP levels, 24-hour ambulatory BP, intensity of drug treatment, electrocardiographic and echocardiographic left ventricular mass, symptoms reported by questionnaire, and costs of treatment. RESULTS: At the end of the study (median follow-up, 350 days; interquartile range, 326-409 days), more home BP than office BP patients had stopped antihypertensive drug treatment (25.6% vs 11.3%; P<.001) with no significant difference in the proportions of patients progressing to multiple-drug treatment (38.7% vs 45.1%; P =.14). The final office, home, and 24-hour ambulatory BP measurements were higher (P<.001) in the home BP group than in the office BP group. The mean baseline-adjusted systolic/diastolic differences between the home and office BP groups averaged 6.8/3.5 mm Hg, 4.9/2.9 mm Hg, and 4.9/2.9 mm Hg, respectively. Left ventricular mass and reported symptoms were similar in the 2 groups. Costs per 100 patients followed up for 1 month were only slightly lower in the home BP group (3875 vs 3522 [4921 dollars vs 4473 dollars]; P =.04). CONCLUSIONS: Adjustment of antihypertensive treatment based on home BP instead of office BP led to less intensive drug treatment and marginally lower costs but also to less BP control, with no differences in general well-being or left ventricular mass. Self-measurement allowed identification of patients with white-coat hypertension. Our findings support a stepwise strategy for the evaluation of BP in which self-measurement and ambulatory monitoring are complementary to conventional office measurement and highlight the need for prospective outcome studies to establish the normal range of home-measured BP.