Ambulatory blood pressure monitoring, European guideline targets, and cardiovascular outcomes: an individual patient data meta-analysis

Abstract

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.

Keywords: Ambulatory blood pressure; Guidelines; Morbidity; Mortality; Population science; Risk stratification.

Structured Graphical Abstract

Figure 1

Relation of office blood pressure with the percentage of time that the 24–h ambulatory blood pressure is within target range according to the 2024 European Society of Cardiology guidelines. The probability that individuals belong to one of four decreasing quartiles of 24–h percentage of time with non-elevated ambulatory blood pressure is assessed by multinomial logistic regression analysis over a wide range of systolic (A, B) and diastolic (C, D) office blood pressure in untreated (A, C) and treated (B, D) study participants. Q1 reflects the worst control of the 24–h ambulatory blood pressure and Q4 the best control. The analysis includes the baseline blood pressure data from 14 230 study participants, of whom 3775 were taking antihypertensive drugs. The non-elevated 24–h ambulatory blood pressure is <115 mmHg systolic and <65 mmHg diastolic. For quartile limits, see Table 1. ODBP, diastolic office blood pressure; OSBP, systolic office blood pressure; PTTR, percentage of time that the 24-h blood pressure is within the target range

Figure 2

Time-dependent receiver operator characteristic curves for the co-primary endpoints in relation to the percentage of time with non-elevated 24–h ambulatory blood pressure. The non-elevated 24–h ambulatory blood pressure is <115 mmHg systolic and <65 mmHg diastolic. The area under the curve for total mortality (A) and the co-primary cardiovascular endpoint (B) increases with longer follow-up, because of the accrual of deaths and cardiovascular endpoints. The number of participants at risk and the number of deaths or cardiovascular endpoints is tabulated for 5-year intervals. The area under the curve is plotted for three models: (i) the base model including cohort (random effect), sex, age, body mass index, smoking and drinking, the total-to-HDL serum cholesterol ratio, antihypertensive drug treatment, and history of cardiovascular disease; (ii) the base model extended by the residual of 24–h mean arterial pressure regressed on percentage of time that the 24-h blood pressure is within the target range (R_MAP); and (iii) the base model extended by the residual of 24-h mean arterial pressure regressed on percentage of time that the 24-h blood pressure is within the target range (R_MAP) and percentage of time that the 24-h blood pressure is within the target range (PTTR). The insert is a magnification of the three plotted lines at 15 years of follow-up. The full model including covariables, 24–h residual of mean arterial pressure and 24–h percentage of time with non-elevated ambulatory blood pressure results in a significantly greater area under the curve compared with both other models (P < .001). AUC, area under the curve; PTTR, percentage of time that the 24-h blood pressure is within the target range; R_MAP, residual of mean arterial pressure regressed on PTTR

Figure 3

Association between the risk of the co-primary endpoints and the percentage of time with non-elevated or non-hypertensive 24-h ambulatory blood pressure. Hazard ratios are obtained by cubic spline regression for total mortality (A, B) and the co-primary cardiovascular endpoint (C, D). The non-elevated 24-h ambulatory blood pressure is currently <115/65 mmHg (A, C), while the 2018 European Society of Cardiology/European Society of Hypertension non-hypertensive 24-h ambulatory blood pressure, which includes the elevated 24–h ambulatory blood pressure, is <130/80 mmHg (B, D). Hazard ratios are adjusted for cohort (random effect), sex, age, body mass index, smoking and drinking, the total-to-HDL serum cholesterol ratio, antihypertensive drug treatment, diabetes, history of cardiovascular disease, and the residual of 24-h mean arterial pressure regressed on percentage of time that the 24-h blood pressure is within the target range. Shaded bands represent the 95% confidence interval of the regression line and grey bars the distribution of 24–h percentage of time with non-elevated ambulatory blood pressure (number of individuals). P-linear and P-non-linear indicate the significance of the linear and non-linear model components. The 2024 European Society of Cardiology non-elevated 24–h percentage of time with non-elevated ambulatory blood pressure, compared with the 2018 European Society of Cardiology/European Society of Hypertension non-hypertensive 24–h percentage of time with non-elevated ambulatory blood pressure, shortened the interval required to reduce relative risk from 60% to 18% (14.4–4.3 h). CI, confidence interval; HR, hazard ratio; 24-h PTTR, percentage of time that 24-h ambulatory blood pressure is within the target range