The Difference in Blood Pressure Between Arms and Survival
The Difference in Blood Pressure Between Arms and Survival
Of 273 patients (14.3% of surgery list) eligible for inclusion, 247 (90%) were recruited by June 2002 and 230 (84%) with complete data were analysed (Figure 1). No participants were lost to follow-up. Participants not included in the analysis were significantly older but did not differ in any other respect from the cohort analysed ( Table 1 ). The median time to collection of all three sets of readings was four months (interquartile range 2-12 months). At recruitment, 55 (24%) participants had a mean interarm difference in systolic blood pressure of 10 mm Hg or more and 21 (9%) a difference of 15 mm Hg or more (Figure 2); 14 (6%) participants had an interarm difference in diastolic blood pressure of 10 mm Hg or more. The mean difference in systolic blood pressure was 1.5 mm Hg (95% confidence interval 0.4 to 2.6) higher in the right arm and in diastolic blood pressure was 1.7 mm Hg (1.1 to 2.3) higher in the left arm.
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Figure 1.
Flow of participants through study
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Figure 2.
Distribution of interarm difference (mean of right arm minus mean of left arm) in systolic blood pressure (SBP) in study sample of 230 people with hypertension
The median time to final analysis or to a fatal event was 9.8 years (interquartile range 0.4-11.4 years). During the study period, 52 cardiovascular and 27 cerebrovascular events occurred in 76 participants. Fifty nine participants died and a total of 100 (44%) participants had an event or died.
There were no differences in the baseline characteristics of participants above and below an interarm difference in systolic blood pressure of 10 mm Hg or more or 15 mm Hg or more or an interarm difference in diastolic blood pressure of 10 mm Hg or more ( Table 2 ).
In both unadjusted and adjusted analyses an interarm difference in systolic blood pressure of 10 mm Hg or more and 15 mm Hg or more were both associated with increases in the hazard of cardiovascular events, cardiovascular mortality, all cause mortality, and combined non-fatal events or all cause mortality. Hazard ratios for all cause mortality after full adjustment were 3.6 (95% confidence interval 2.0 to 6.5) for interarm differences in systolic blood pressure of 10 mm Hg or more (Figure 3) and 3.1 (1.6 to 6.0) for differences of 15 mm Hg or more ( Table 3 ). This corresponded to a 5-6% increase in the hazard of outcomes for each 1 mm Hg increment in interarm difference for systolic blood pressure ( Table 4 ). An interarm difference in diastolic blood pressure of 10 mm Hg or more was associated, with less precision, with increases in the hazard of cardiovascular events and combined non-fatal events or all cause mortality in both unadjusted and adjusted analyses: adjusted hazard ratios 3.8 (95% confidence interval 1.8 to 8.6) and 3.3 (1.6 to 6.8), respectively. After adjustment this corresponded to a 9% increase in hazard of any fatal or non-fatal event for each 1 mm Hg increment in interarm difference for diastolic blood pressure. Across all models for systolic blood pressure the likelihood ratio test showed a significant reduction in goodness of fit on removal of interarm difference, with the exception of cardiovascular mortality associated with a difference of 15 mm Hg or more, indicating that inclusion of interarm differences in systolic blood pressure consistently improved the predictability of models. This was also shown for an interarm difference in diastolic blood pressure of 10 mm Hg or more with non fatal events and combined events and deaths ( Table 3 and Table 4 ).
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Figure 3.
Kaplan-Meier plot for all cause mortality in 230 people with hypertension with or without an interarm difference in systolic blood pressure (SBP) of ≥10 mm Hg
At recruitment 183 participants had no pre-existing cardiovascular disease; 28% (n=51) had an interarm difference in systolic blood pressure of 10 mm Hg or more and 11% (n=20) a difference of 15 mm Hg or more, and 6% (n=11) had an interarm difference in diastolic blood pressure of 10 mm Hg or more. In this subgroup, sensitivity analyses of predefined levels of interarm differences in both systolic and diastolic blood pressures were examined for differences in mortality and event free survival. The findings of unadjusted and adjusted Cox regression analyses were consistent with the full case analysis, showing increases in the hazards of cardiovascular events, cardiovascular mortality, all cause mortality, and combined events or deaths in both unadjusted and adjusted analyses for interarm differences in systolic blood pressure of 10 mm Hg or more or 15 mm Hg or more; hazard ratios for all cause mortality were 2.6 (95% confidence interval 1.4 to 4.8; Figure 4) and 2.7 (1.3 to 5.4). An interarm difference in diastolic blood pressure of 10 mm Hg or more was associated with an increased hazard of cardiovascular events, and combined non-fatal events or all cause mortality after adjustment: hazard ratios 3.2 (1.3 to 8.1) and 2.4 (1.0 to 5.9); Table 5 . When interarm difference was analysed as a continuous variable, the hazard of all outcomes increased by a consistent 5% for each 1 mm Hg increment in interarm difference in systolic blood pressure after adjustment. In the continuous model the hazard ratios for an interarm difference in diastolic blood pressure were no longer significant ( Table 4 ). Associated reductions in goodness of fit were seen on removal of interarm differences in systolic blood pressure from the models.
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Figure 4.
Kaplan-Meier plot for all cause mortality in 183 people with hypertension without cardiovascular disease at recruitment, with or without an interarm difference in systolic blood pressure (SBP) of ≥10 mm Hg
In primary prevention of cardiovascular disease a 10 year cardiovascular risk score of more than 20% over 10 years represents a threshold for intervention with statin therapy. Participants without pre-existing cardiovascular disease were therefore stratified by both their conventional risk score (above or below the threshold of 20%) and their interarm difference in systolic blood pressure (above or below 10 mm Hg). Analysis showed that the presence of an interarm difference in systolic blood pressure of 10 mm Hg or more without pre-existing disease, but where the cardiovascular risk score was more than 20%, was associated with a significantly higher hazard of combined fatal and non-fatal events compared with those with an interarm difference in systolic blood pressure of less than 10 mm Hg but equivalent cardiovascular risk score (log rank statistic 25.9, P<0.001) and also a higher hazard when compared with those with pre-existing disease (log rank statistic 4.5, P<0.05; Figure 5).
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Figure 5.
Kaplan-Meier survival curve for fatal and non-fatal events stratified by pre-existing cardiovascular disease (CVD) at recruitment, cardiovascular risk score, and interarm difference in systolic blood pressure (SBP) ≥10 mm Hg (n=230)
Results
Of 273 patients (14.3% of surgery list) eligible for inclusion, 247 (90%) were recruited by June 2002 and 230 (84%) with complete data were analysed (Figure 1). No participants were lost to follow-up. Participants not included in the analysis were significantly older but did not differ in any other respect from the cohort analysed ( Table 1 ). The median time to collection of all three sets of readings was four months (interquartile range 2-12 months). At recruitment, 55 (24%) participants had a mean interarm difference in systolic blood pressure of 10 mm Hg or more and 21 (9%) a difference of 15 mm Hg or more (Figure 2); 14 (6%) participants had an interarm difference in diastolic blood pressure of 10 mm Hg or more. The mean difference in systolic blood pressure was 1.5 mm Hg (95% confidence interval 0.4 to 2.6) higher in the right arm and in diastolic blood pressure was 1.7 mm Hg (1.1 to 2.3) higher in the left arm.
(Enlarge Image)
Figure 1.
Flow of participants through study
(Enlarge Image)
Figure 2.
Distribution of interarm difference (mean of right arm minus mean of left arm) in systolic blood pressure (SBP) in study sample of 230 people with hypertension
The median time to final analysis or to a fatal event was 9.8 years (interquartile range 0.4-11.4 years). During the study period, 52 cardiovascular and 27 cerebrovascular events occurred in 76 participants. Fifty nine participants died and a total of 100 (44%) participants had an event or died.
All Case Analysis
There were no differences in the baseline characteristics of participants above and below an interarm difference in systolic blood pressure of 10 mm Hg or more or 15 mm Hg or more or an interarm difference in diastolic blood pressure of 10 mm Hg or more ( Table 2 ).
In both unadjusted and adjusted analyses an interarm difference in systolic blood pressure of 10 mm Hg or more and 15 mm Hg or more were both associated with increases in the hazard of cardiovascular events, cardiovascular mortality, all cause mortality, and combined non-fatal events or all cause mortality. Hazard ratios for all cause mortality after full adjustment were 3.6 (95% confidence interval 2.0 to 6.5) for interarm differences in systolic blood pressure of 10 mm Hg or more (Figure 3) and 3.1 (1.6 to 6.0) for differences of 15 mm Hg or more ( Table 3 ). This corresponded to a 5-6% increase in the hazard of outcomes for each 1 mm Hg increment in interarm difference for systolic blood pressure ( Table 4 ). An interarm difference in diastolic blood pressure of 10 mm Hg or more was associated, with less precision, with increases in the hazard of cardiovascular events and combined non-fatal events or all cause mortality in both unadjusted and adjusted analyses: adjusted hazard ratios 3.8 (95% confidence interval 1.8 to 8.6) and 3.3 (1.6 to 6.8), respectively. After adjustment this corresponded to a 9% increase in hazard of any fatal or non-fatal event for each 1 mm Hg increment in interarm difference for diastolic blood pressure. Across all models for systolic blood pressure the likelihood ratio test showed a significant reduction in goodness of fit on removal of interarm difference, with the exception of cardiovascular mortality associated with a difference of 15 mm Hg or more, indicating that inclusion of interarm differences in systolic blood pressure consistently improved the predictability of models. This was also shown for an interarm difference in diastolic blood pressure of 10 mm Hg or more with non fatal events and combined events and deaths ( Table 3 and Table 4 ).
(Enlarge Image)
Figure 3.
Kaplan-Meier plot for all cause mortality in 230 people with hypertension with or without an interarm difference in systolic blood pressure (SBP) of ≥10 mm Hg
Analyses Without Pre-existing Cardiovascular Disease
At recruitment 183 participants had no pre-existing cardiovascular disease; 28% (n=51) had an interarm difference in systolic blood pressure of 10 mm Hg or more and 11% (n=20) a difference of 15 mm Hg or more, and 6% (n=11) had an interarm difference in diastolic blood pressure of 10 mm Hg or more. In this subgroup, sensitivity analyses of predefined levels of interarm differences in both systolic and diastolic blood pressures were examined for differences in mortality and event free survival. The findings of unadjusted and adjusted Cox regression analyses were consistent with the full case analysis, showing increases in the hazards of cardiovascular events, cardiovascular mortality, all cause mortality, and combined events or deaths in both unadjusted and adjusted analyses for interarm differences in systolic blood pressure of 10 mm Hg or more or 15 mm Hg or more; hazard ratios for all cause mortality were 2.6 (95% confidence interval 1.4 to 4.8; Figure 4) and 2.7 (1.3 to 5.4). An interarm difference in diastolic blood pressure of 10 mm Hg or more was associated with an increased hazard of cardiovascular events, and combined non-fatal events or all cause mortality after adjustment: hazard ratios 3.2 (1.3 to 8.1) and 2.4 (1.0 to 5.9); Table 5 . When interarm difference was analysed as a continuous variable, the hazard of all outcomes increased by a consistent 5% for each 1 mm Hg increment in interarm difference in systolic blood pressure after adjustment. In the continuous model the hazard ratios for an interarm difference in diastolic blood pressure were no longer significant ( Table 4 ). Associated reductions in goodness of fit were seen on removal of interarm differences in systolic blood pressure from the models.
(Enlarge Image)
Figure 4.
Kaplan-Meier plot for all cause mortality in 183 people with hypertension without cardiovascular disease at recruitment, with or without an interarm difference in systolic blood pressure (SBP) of ≥10 mm Hg
Stratified Analysis
In primary prevention of cardiovascular disease a 10 year cardiovascular risk score of more than 20% over 10 years represents a threshold for intervention with statin therapy. Participants without pre-existing cardiovascular disease were therefore stratified by both their conventional risk score (above or below the threshold of 20%) and their interarm difference in systolic blood pressure (above or below 10 mm Hg). Analysis showed that the presence of an interarm difference in systolic blood pressure of 10 mm Hg or more without pre-existing disease, but where the cardiovascular risk score was more than 20%, was associated with a significantly higher hazard of combined fatal and non-fatal events compared with those with an interarm difference in systolic blood pressure of less than 10 mm Hg but equivalent cardiovascular risk score (log rank statistic 25.9, P<0.001) and also a higher hazard when compared with those with pre-existing disease (log rank statistic 4.5, P<0.05; Figure 5).
(Enlarge Image)
Figure 5.
Kaplan-Meier survival curve for fatal and non-fatal events stratified by pre-existing cardiovascular disease (CVD) at recruitment, cardiovascular risk score, and interarm difference in systolic blood pressure (SBP) ≥10 mm Hg (n=230)