Outcome-driven thresholds for ambulatory pulse pressure in 9938 participants recruited from 11 populations

Abstract

Evidence-based thresholds for risk stratification based on pulse pressure (PP) are currently unavailable. To derive outcome-driven thresholds for the 24-hour ambulatory PP, we analyzed 9938 participants randomly recruited from 11 populations (47.3% women). After age stratification (<60 versus ≥60 years) and using average risk as reference, we computed multivariable-adjusted hazard ratios (HRs) to assess risk by tenths of the PP distribution or risk associated with stepwise increasing (+1 mm Hg) PP levels. All adjustments included mean arterial pressure. Among 6028 younger participants (68 853 person-years), the risk of cardiovascular (HR, 1.58; P=0.011) or cardiac (HR, 1.52; P=0.056) events increased only in the top PP tenth (mean, 60.6 mm Hg). Using stepwise increasing PP levels, the lower boundary of the 95% confidence interval of the successive thresholds did not cross unity. Among 3910 older participants (39 923 person-years), risk increased (P≤0.028) in the top PP tenth (mean, 76.1 mm Hg). HRs were 1.30 and 1.62 for total and cardiovascular mortality, and 1.52, 1.69, and 1.40 for all cardiovascular, cardiac, and cerebrovascular events. The lower boundary of the 95% confidence interval of the HRs associated with stepwise increasing PP levels crossed unity at 64 mm Hg. While accounting for all covariables, the top tenth of PP contributed less than 0.3% (generalized R(2) statistic) to the overall risk among the elderly. Thus, in randomly recruited people, ambulatory PP does not add to risk stratification below age 60; in the elderly, PP is a weak risk factor with levels below 64 mm Hg probably being innocuous.

Keywords: ambulatory blood pressure; epidemiology; population science; pulse pressure.

Figure 1. Hazard ratios in tenths of the distribution of 24–h pulse pressure in 6028 younger participants

Hazard ratios for total (A) and cardiovascular (B) mortality and for cardiovascular (C) and cardiac (D) events express the risk in each tenth compared with average risk. Hazard ratios were adjusted for cohort, sex, age, 24–h mean arterial pressure, 24–h heart rate, body mass index, smoking and drinking, serum cholesterol, history of cardiovascular disease and diabetes, antihypertensive drug treatment. Vertical bars denote 95% confidence intervals. For each tenth, the number of events and unadjusted incidence rates (in percent) are given. The P value refers to the significance of the hazard ratio in the top tenth of the 24–h pulse pressure distribution.

Figure 2. Hazard ratios in tenths of the distribution of 24–h pulse pressure in 3910 older participants

Hazard ratios for total (A) and cardiovascular (B) mortality and for cardiovascular (C) and cardiac (D) events express the risk in each tenth compared with average risk. The hazard ratios were adjusted as in Figure 1. Vertical bars denote 95% confidence intervals. For each tenth, the number of events and unadjusted incidence rates (in percent) are given. The P value refers to the significance of the hazard ratio in the top tenth of the 24–h pulse pressure distribution.

Figure 3. Hazard ratios according to 24–h pulse pressure levels ranging from the 10th to the 90th percentile in 3910 older participants

Hazard ratios for total mortality (A) and cardiovascular (B) mortality and for cardiovascular (C) and cardiac (D) events express the risk at each level of pulse pressure compared with average risk. Solid and dotted lined denote the point estimates and the 95% confidence intervals, respectively. The hazard ratios were adjusted as in Figure 1.

Figure 4. Multivariable-adjusted hazard ratios for outcomes in relation to 24–h (A), daytime (B), nighttime (C), and conventional (D) pulse pressure in 3910 older participants

The hazard ratios, presented with 95% confidence interval (CI), express the risk in the top tenth compared with the average risk in the participants. Pulse pressure thresholds delineating the top tenth were ≥68.8, ≥71.3, ≥66.8, and ≥80.0 mm Hg for 24–h, daytime, nighttime and conventional blood pressure measurement; the corresponding mean levels of pulse pressure in the top tenth were 76.1, 78.8, 75.6 and 89.0 mm Hg, respectively. All models were adjusted for cohort, sex, age, mean arterial pressure and heart rate (on 24–h, daytime, nighttime, conventional measurement in panels A, B, C, and D, respectively), body mass index, smoking and drinking, serum cholesterol, history of cardiovascular disease and diabetes, and antihypertensive drug treatment. P values are for the risk in the top tenth relative to the overall risk in the whole study population. CV denotes cardiovascular. E/R1–9 and E/R10 indicate the number of events and participants at risk below the 90th percentile of the pulse pressure distribution and in the top tenth, respectively.