Dong-Yan Zhang

BACKGROUND: Whether central systolic blood pressure (cSBP) compared with brachial systolic blood pressure (bSBP) improves risk stratification remains debated. This study investigated whether cSBP is more closely associated with total and cardiovascular mortality than bSBP when recorded by 24-hour ambulatory BP monitoring with an arm cuff-based oscillometric monitor. METHODS: Consecutive patients referred for ambulatory BP monitoring and enrolled in the Shanghai Ruijin Ambulatory BP Monitoring Registry (2017–2023) were analyzed. bSBP and cSBP were recorded over 24 hours. cSBP was calibrated on brachial systolic and diastolic BP (cSBPc1) or on mean arterial pressure and brachial diastolic BP (cSBPc2). Total and cardiovascular mortality up to December 31, 2024, was assessed by record linkage with International Classification of Diseases, Tenth Revision , coded death certificates. Linear and nonlinear Cox proportional hazard regression was applied with age as the underlying time-scale and adjusted for established cardiovascular risk factors. RESULTS: Over 4.0 years of follow-up, 505 of 36 594 participants (52.8% women; median age, 53.4 years) died, 174 from cardiovascular disease. With multivariable adjustment applied, the nonlinear compared with linear Cox models provided a better model fit for both end points ( P P ≤0.06). Adding cSBPc1 or cSBPc2 to the base model extended by bSBP also increased the C statistics, but not by a statistically significant amount (0.054≤ P ≤0.22). CONCLUSIONS: cSBP compared with bSBP did not improve the associations with mortality. Measurement of the ambulatory bSBP is adequate for BP-based risk stratification.

BACKGROUND: The ambulatory arterial stiffness index (AASI) is increasingly used in clinical research and practice. This individual-participant meta-analysis aims to consolidate the prognostic accuracy of AASI in the general population and to derive an end point–based AASI risk threshold. METHODS: In 12 558 individuals enrolled in 14 population studies (48.8% women; mean age, 59.3 years), AASI was derived by regressing 24-hour diastolic on systolic blood pressure (mm Hg/mm Hg). Using Cox regression, the risk-carrying AASI threshold was established by examining stepwise increasing AASI levels and by determining the AASI level, yielding a 10-year risk similar to an office systolic pressure of 140 mm Hg. RESULTS: Over 10.7 years (median), 3027 all-cause deaths and 2183 cardiovascular end points occurred. In all participants, multivariable-adjusted hazard ratios expressing the all-cause deaths and cardiovascular end point risk per 1-SD AASI increment were 1.08 (95% CI, 1.04–1.13) and 1.13 (95% CI, 1.07–1.18). In a randomly defined subset of 8189 individuals, the risk-carrying AASI thresholds converged to 0.50 with hazard ratios (≥0.50 versus <0.50) of 1.14 (95% CI, 1.04–1.26) for all-cause deaths and 1.13 (95% CI, 1.01–1.26) for cardiovascular end point. In the replication sample (n=4369), these hazard ratios were 1.13 (95% CI, 1.01–1.26) and 1.19 (95% CI, 1.04–1.35). AASI continuous or per threshold significantly improved model performance. Analyses of secondary end points and subgroups stratified by sex, age, hypertension status and treatment, history of cardiovascular disease, and nocturnal dipping were confirmatory. CONCLUSIONS: Over and beyond traditional risk factors, AASI improves risk stratification. Exceeding the risk-carrying 0.50 AASI threshold necessitates increased vigilance in managing risk factors before irreversible cardiovascular complications occur.

BACKGROUND: Epidemiological evidence suggests higher rates of heart failure in adults born at an extremely low birth weight (ELBW). Reports on the echocardiographic phenotype in this population are inconsistent and do not consider the effect of modifiable contributors such as blood pressure. METHODS: This study reports on the echocardiographic findings of the PREMATurity as predictor of children's Cardiovascular-renal Health (PREMATCH) study, a prospective case-control study evaluating renal and cardiovascular outcomes in children with ELBW in comparison to term-born controls. Left ventricular (LV) mass was the primary outcome. Data were analyzed with multivariable-adjusted regression models considering anthropometric variables and systolic blood pressure as covariates. RESULTS: Eighty cases (median age, 10.8 years) and 72 controls (median age, 11.4 years) were included. Multivariable-adjusted analyses revealed that the adjusted difference in LV mass in cases versus controls was −8.49 g (CI, −13.78 to −3.20; P =0.002). Sex, height, weight, and body fat percentage were significant covariates. There was a positive interaction between ELBW status and systolic blood pressure ( P _interaction =0.039). There was a −6.47 g (CI, −11.7 to 1.28; P =0.016) difference in LV mass between normotensive cases and controls, while the difference disappeared between subjects with increased blood pressure or hypertension. CONCLUSIONS: ELBW children exhibit lower LV mass during childhood in comparison with term-born controls. However, elevations in systolic blood pressure are associated with a steeper increase in LV mass in cases than in controls. Our findings question whether cutoffs for the general population are adequate to evaluate and manage hypertension and LV hypertrophy in children with ELBW.

Introduction: Biological rather than chronological age (C-age) drives deviation from healthy aging. This study aimed to identify a plasma metabolomic signature indicative of age-related cardiovascular risk (pMTB-age) predicting vascular morbidity and mortality. Methods: Nuclear magnetic resonance identified 38 plasma metabolites in two population cohorts: the Flemish cohort examined as discovery (N = 719 [2005–2010]) and internal replication cohort (N = 580/719 [2009–2013]) and the external replication Spanish Hortega cohort (N = 811 [2001]). Results: The trained model (pMTB-age), relating C-age to the plasma metabolome derived by elastic net regression, included 18 metabolites (six amino acids) and explained from 28.6% to 22.9% of C-age in the discovery and replication data. Feature importance of the retained metabolites derived by SHapley Additive exPlanation showed large interindividual variability in the relation between C-age and pMTB-age. In Flemish and Spanish, cardiovascular risk factors were significantly associated with C-age, pMTB-age, and pMTB-age uncorrelated from C-age (pMTB-age-R). In Flemish (median follow-up 12.3 years) and Spanish (18.8 years), mortality and cardiovascular complications correlated with C-age and pMTB-age. In Flemish, cardiac endpoints (hazard ratio [95% CI] 1.28 [1.00–1.63]) and its components kept significance in relation to pMTB-age-R. The pathway analysis revealed overrepresentation of glycine, serine, and threonine. Conclusions: pMTB-age is a multidimensional biomarker, which identifies individuals with accelerated vascular aging with high precision and combined with the pathway analysis highlights the role of amino acids in vascular disease. Therefore, pMTB-age can guide risk stratification and the personalized and timely prevention and treatment tailored to an individual’s unique pMTB-age profile.

Glomerular filtration rate (eGFR) derived from serum creatinine (eGFR_cr), cystatin C (eGFR_cys), or both (eGFR_cr-cys) by race-free equations are recommended staging chronic kidney disease (CKD). The current study aimed to compare these race-free eGFR equations for screening for low-grade CKD in Blacks and non-Blacks and to evaluate their association with mortality. Race-free eGFR equations were evaluated in four studies with specific inclusion criteria based on the original research goals: African-PREDICT (341/380 healthy Black/White South Africans), FLEMENGHO (709 White community-dwelling Flemish), NHANES (1760/7931 Black and non-Black adult Americans), and 401 Black African patients hospitalised in Mbuji Mayi, Democratic Republic of Congo. The intraclass correlation coefficient and Bland and Altman statistics were used to assess consistency between eGFR equations and multivariable logistic or Cox regression to evaluate their association with mortality. Intraindividual discordance between eGFRs was larger in Black than non-Black NHANES and African-PREDICT participants. In NHANES, eGFR_cr-cys was greater than eGFR_cr, but smaller than eGFR_cys, and replacing eGFR_cr-cys by eGFR_cr moved 25% Blacks and 15% non-Blacks to a higher (worse) eGFR KDIGO stage. In African-PREDICT and FLEMENGO, half of the measured creatinine clearance to eGFR ratios fell outside the expected 1.1-1.2 band. In NHANES, multivariable hazard ratios for total and cardiovascular mortality in relation to CKD grade were all lower than unity for grade-1 CKD and greater than unity for grade ≥3 (p < 0.0001) without any racial difference (0.11 ≤ p ≤ 0.98). These NHANES findings were consistent, if CKD stage was replaced by eGFR and in subgroup analyses. Whereas eGFR_cys and eGFR_cr-cys refined models, eGFR_cr did not. The NHANES mortality outcomes support the use of eGFR_cys and eGFR_cr-cys. However, large intraindividual variability between eGFR estimates may lead to KDIGO eGFR stage misclassification and calls for caution in the opportunistic or systematic screening for CKD in asymptomatic individuals with prevention as objective.

BACKGROUND: This study assessed the presence of intracranial arterial stenosis (ICAS) in relation to home systolic blood pressure (SBP) and its variability (BPV). METHODS: In 1510 untreated patients, ICAS was assessed by transcranial Doppler ultrasonography. SBP and BPV were determined from individual home BP recordings over seven days with triplicate readings in the morning and evening. BP variability was expressed as standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV). CV was SD divided by the mean, VIM was SD divided by the mean to the power x and multiplied by the population mean to the power x, and ARV reflected the average absolute difference between consecutive BP readings. Associations with ICAS were assessed from nested multivariable logistic models. RESULTS: One hundred and fourteen participants (7.5%) had ICAS. Combining all BP readings, SBP, SD, CV, VIM, and ARV averaged (± between-patient SD) 130.1 ± 11.9 mm Hg, 8.36 ± 2.53 mm Hg, 6.42 ± 1.83%, 8.36 ± 2.38, and 6.41 ± 1.61 mm Hg, respectively. In multivariable-adjusted models, higher home SBP was independently associated with increased prevalence of ICAS. For morning measurements, all variability indices were significantly associated with ICAS, with odds ratios per 1-SD increase ranging from 1.33 to 1.34 (P ≤ 0.005), independent of SBP level. In contrast, associations based on evening variability were non-significant. Sex and anatomical ICAS location did not impact these results. CONCLUSIONS: The prevalence of ICAS was positively associated with SBP level. In addition to the SBP level, all four morning BPV indexes refined the assessment of ICAS prevalence.

Background and Aims: Hypertension is the predominant modifiable cardiovascular risk factor. This cohort study assessed the association of risk with the percentage of time that the ambulatory blood pressure (ABP) is within the target range (PTTR) proposed by the 2024 European Society of Cardiology (ESC) guidelines for blood pressure (BP) management. Methods: In a person-level meta-analysis of 14 230 individuals enrolled in 14 population cohorts, systolic and diastolic ABPs were combined to assess 24-h, daytime, and nighttime PTTR with thresholds for non-elevated ABP set at <115/65, <120/70, and <110/60 mmHg, respectively. Results: Median 24-h PTTR was 18% (interquartile range 5–33) corresponding to 4.3 h (1.2–7.9). Over 10.9 years (median), deaths (N = 3117) and cardiovascular endpoints (N = 2265) decreased across increasing 24-h PTTR quartiles from 21.3 to 16.1 and from 20.3 to 11.3 events per 1000 person-years. The standardized multivariable-adjusted hazard ratios for 24-h PTTR were 0.57 (95% confidence interval 0.46–0.71) for mortality and 0.30 (0.23–0.39) for cardiovascular endpoints. Analyses of daytime and nighttime ABP, cardiovascular mortality, coronary endpoints and stroke, and subgroups produced confirmatory results. The 2024 ESC non-elevated 24-h PTTR, compared with the 2018 ESC/European Society of Hypertension non-hypertensive 24-h PTTR, shortened the interval required to reduce relative risk for adverse outcomes from 60% to 18% (14.4–4.3 h). Office BP, compared with 24-h PTTR, misclassified most participants with regard to BP control. Conclusions: Longer time that ABP is within the 2024 ESC target range is associated with reduced adverse outcomes; PTTR derived from ABP refines risk prediction and compared with office BP avoids misclassification of individuals with regard to BP control.