Within-subject blood pressure level--not variability--predicts fatal and nonfatal outcomes in a general population

Abstract

To assess the prognostic significance of blood pressure (BP) variability, we followed health outcomes in a family-based random population sample representative of the general population (n=2944; mean age: 44.9 years; 50.7% women). At baseline, BP was measured 5 times consecutively at each of 2 home visits 2 to 4 weeks apart. We assessed within-subject overall (10 readings), within- and between-visit systolic BP variability from variability independent of the mean, the difference between maximum and minimum BP, and average real variability. Over a median follow-up of 12 years, 401 deaths occurred and 311 participants experienced a fatal or nonfatal cardiovascular event. Overall systolic BP variability averaged (SD) 5.45 (2.82) units, 15.87 (8.36) mmHg, and 4.08 (2.05) mmHg for variability independent of the mean, difference between maximum and minimum BP, and average real variability, respectively. Female sex, older age, higher-mean systolic BP, lower body mass index, a history of peripheral arterial disease, and use of β-blockers were the main correlates of systolic BP variability. In multivariable-adjusted analyses, overall and within- and between-visit BP variability did not predict total or cardiovascular mortality or the composite of any fatal plus nonfatal cardiovascular end point. For instance, the hazard ratios for all cardiovascular events combined in relation to overall variability independent of the mean, difference between maximum and minimum BP, and average real variability were 1.05 (0.96-1.15), 1.06 (0.96-1.16), and 1.08 (0.98-1.19), respectively. By contrast, mean systolic BP was a significant predictor of all end points under study, independent of BP variability. In conclusion, in an unbiased population sample, BP variability did not contribute to risk stratification over and beyond mean systolic BP.

Figure 1

Systolic blood pressure (SBP) on repeated measurement. Nurses measured blood pressure 5 times consecutively at each of 2 home visits 2 to 4 weeks apart. Values are means (±SE) of single readings or of all (n=5) readings obtained in 2944 participants at the first (open bars) or second (shaded bars) home visit. Numbers along the horizontal axis denote the order of the measurements or visits. An asterisk indicates a significant difference (P<0.0001) with the adjacent mean systolic blood pressure.

Figure 2

Frequency distribution of overall variability of systolic blood pressure independent of the mean. Overall variability is based on 10 blood pressure readings in 2944 participants, that is, 5 at each of 2 home visits. The P value is for departure of the actually observed distribution (full line) from normality (dotted line). S indicates the coefficient of skewness; K, the coefficient of kurtosis.

Figure 3

Mortality (A and B) and cardiovascular (CV) events (C and D) by quartiles of the distribution of mean systolic blood pressure (SBP) and overall variability independent of the mean (VIM) in 2944 participants. Incidence rates were standardized for sex and age by the direct method. The number of end points contributing to the rates is presented. The trend across quartiles of systolic pressure (A and C) was significant for total mortality (P<0.0001), non-CV mortality (P=0.044), CV mortality (P<0.0001), all CV events (P<0.0001), cardiac events (P<0.0001), and stroke (P=0.0001). The trends across quartiles of overall VIM (B and D) were all nonsignificant (P≥0.58).

Figure 4

Kaplan-Meier survival function estimates for total mortality (A and C) and cardiovascular (CV) events (B and D) by sex-specific quartiles of mean systolic blood pressure (SBP) and overall systolic variability independent of the mean (VIM). CV events include all of the fatal and nonfatal CV end points. P values refer to the significance of the log-rank test across 4 quartiles.

Figure 5

Absolute 10-year risk of death (A) or a cardiovascular (CV) event (B) in relation to mean systolic blood pressure (SBP) at different levels of overall systolic variability independent of the mean (VIM). Mean systolic blood pressure along the x axis covers the 5th to 95th percentile interval. The variability independent of the mean is presented by 4 risk functions corresponding with 2, 4, 6, and 9 units (approximate quartile midpoints). The risk functions were standardized to the distributions (mean or ratio) of sex, age, body mass index, heart rate, smoking and drinking, total:high-density lipoprotein serum cholesterol ratio, plasma glucose, history of CV disease, and use of β-blockers. Among 2944 participants, 401 deaths and 311 composite CV end points occurred. P_SBP and P_VIM indicate the significance of mean systolic blood pressure and the overall variability independent of the mean.