Increased pulse pressure (PP) is a predictor of adverse cardiovascular events in the general population,1–9 and in patients after coronary artery bypass graft (CABG) surgery.10 Whereas PP >80 mm Hg increased the incidence of congestive heart failure (CHF) by 52% and death from a cardiac cause by 100%, even PP increments of 10 mm Hg (above a threshold of 40 mm Hg) were associated with 12% increased risk of cerebral events after CABG surgery.10 Increased PP has also been associated with poor long-term survival after CABG surgery.11
Increased systolic blood pressure predisposes to left ventricular hypertrophy,12 diastolic dysfunction, increased myocardial oxygen demand, and subsequent left ventricular failure.13,14 Lower diastolic pressure decreases coronary perfusion and predisposes to ischemia,15 and thus these patients are at risk for both poor short-term10 and long-term outcomes.16 Patients with peripheral arterial disease often have coronary artery disease15,17 and are at risk for postoperative major adverse cardiovascular events (MACEs). Increased PP is a manifestation of increased arterial stiffness and an increased central aortic pressure. It is unknown whether PP from limb blood pressure measurements can truly characterize the central aortic stiffness and serve as a marker for MACEs after peripheral vascular surgery. If PP can reliably predict MACE risk in the latter population, it may help improve existing risk indices and possibly enable strategies to reduce morbidity and health care resource utilization for affected patients.18 An example of such an approach is preoperative hemodynamic optimization that has been consistently shown to reduce postoperative morbidity and hospital length of stay.19,20 The purpose of this study was to test the hypothesis that increased preoperative PP predicts MACEs after lower extremity revascularization surgery.
After IRB approval (waived informed consent as a part of retrospective medical record and database review; data analysis was HIPAA [Health Insurance Portability and Accountability Act] compliant), we used the prospectively collected vascular surgery database at our institution to identify 412 consecutive patients who had lower extremity bypass surgery from January 2003 to December 2004. Patients with abdominal aortic aneurysm repairs, carotid endarterectomy, major vascular amputations, and varicose vein procedures were excluded from the analysis to homogenize the surgical risk. Repeat peripheral vascular bypass procedures during the study period were also excluded from the analysis. Preoperative demographics, comorbid conditions, medications, intraoperative data, and postoperative outcomes were recorded in this prospective database. Dedicated trained research nurses collected the postoperative outcome data. Two physicians agreed on each identified outcome before it was coded in the surgical quality assurance database. MACEs were predefined using the following criteria. Medical records were reviewed to record systolic and diastolic blood pressure from the preoperative surgical visit, preoperative anesthesia evaluation, and/or surgical floor reading the night before surgery for inpatients. PP was calculated as the difference of systolic and diastolic blood pressure. Final PP was obtained from the average of the available preoperative recordings. The secondary outcome of interest was in-hospital length of stay expressed as mean ± SD (days).
- Myocardial infarction (MI): the presence of (a) troponin-T level >0.1 ng/mL; (b) new Q waves, horizontal or down-sloping ST segment depression of at least 0.1 mV, or ST elevation of at least 0.15 mV; or (c) chest pain (diagnosis required 2 of 3 criteria). The electrocardiograms were read by both a cardiology fellow and attending physician. The attending cardiology physician determination on the electrocardiogram was final if there was no consensus. Patients received troponin tests only if there was a clinical suspicion of myocardial ischemia.
- CHF: required clinical and radiological evidence of pulmonary edema that required diuresis and supplemental oxygen by facemask or endotracheal intubation.
- Stroke: clinical and radiological evidence of stroke or transient ischemic attack. The neurologist's diagnosis was taken as the final word for outcome.
The primary outcome of this study was MACE defined as MI, CHF, stroke, or in-hospital cardiac death. PP and demographic data were described as mean ± SD for continuous data and percent for categorical data. Normality for PP data was tested with the Shapiro-Wilk test. The distribution of perioperative characteristics regarding PP and MACEs was tested with univariate analysis to identify confounders for the final multivariable logistic regression analysis. PP data were then tested as categorical data (quartiles, mean, median, and PP <80 or ≥80 mm Hg as described previously) to predict postoperative outcomes, in a sequential manner. All preoperative demographics were compared between the 2 groups (high/low PP or MACEs with and without) with 2-sided t test with unequal variances for continuous variables and Fisher exact test or χ2 for categorical variables. The confounders were identified if they interacted with MACEs and PP. A final logistic regression (backward) was built with the confounders if their univariate significance was less than P < 0.2. P < 0.05 was considered statistically significant. SPSS 15.0 software (SPSS, Inc., Chicago, IL) was used for the statistical analysis.
Overall Population Characteristics
Of the 412 patients, 65% had all 3 preoperative blood pressure readings whereas the remainder had 1 or 2 readings; this was expected, because many patients were not admitted before surgery. PPs were averaged for those with 2 or 3 preoperative blood pressure recordings. No further analysis was done between the subgroups of complete (3 sets of preoperative blood pressure data) and incomplete (1 or 2 preoperative blood pressure) data in this retrospective, exploratory data analysis.
The average age of this cohort was 69 ± 12 years and systolic and diastolic blood pressures were 140 ± 21 mm Hg and 69 ± 13 mm Hg, respectively. PP data were normally distributed and are shown in Figure 1. The average PP was 71 ± 21 mm Hg and the median (interquartile range [IQR]) PP was 70 (57, 85) mm Hg.
Identifying Appropriate PP Cutoff for the Prediction Model
Previous studies have shown PP of 40 and 80 mm Hg10,11 as cutoffs associated with short- and long-term adverse outcomes. The majority of patients in our study had a PP >40 mm Hg (median [IQR] was 70 [57, 85] mm Hg) (Fig. 1). Therefore, a PP of 80 mm Hg was used as a cutoff for the prediction model. PP as a continuous predictor was formally tested in the final multivariable regression model. A receiver operating characteristic curve for PP against MACE outcomes showed an insignificant area under the curve of 0.556 (P = 0.323) (Fig. 2). There was no interaction between age and PP. PP was further divided into 4 equal quartiles. There was no relation between MACEs and PPs within each age quartile (≤59 years [n = 106, P = 0.55], 60–69 years [n = 101, P = 0.80], 70–78 years [n = 107, P = 0.61], and 79+ years [n = 97, P = 0.08]).
Patient Characteristics When Split by PP ≥80 mm Hg
The demographic information for patients with a PP ≥80 mm Hg compared with patients with a PP <80 mm Hg is listed in Table 1. Patients with a PP ≥80 mm Hg were older and were more likely to have insulin-treated diabetes. Other preoperative cardiovascular risk factors such as history of coronary artery disease, MI, CHF, stroke, chronic renal failure, and smoking were similar between the 2 groups (Table 1). Preoperative uses of aspirin, “statin” drugs, or β-blockers, as well as intraoperative β-blockade, were similar between the 2 groups (Table 1).
The frequency of MACEs based on PP categories is shown in Table 2. MACEs occurred in 5.7% of patients in the PP <80 mm Hg group compared with 8.8% of the PP ≥80 mm Hg group (P = 0.229). Individual MACE outcomes such as MI, CHF, stroke, and in-hospital cardiac death were similar.
Univariate Analysis of Perioperative Variables with MACE Outcomes
Nine percent of patients with a history of MI had MACEs compared with 4% of patients without a history of MI (P = 0.049). There were no gender differences (7% men and 6% women, P = 0.843) between patients with and without MACEs. Other factors such as CHF (P = 0.20), hypertension (P = 0.803), diabetes mellitus (P = 0.543), insulin-treated diabetes mellitus (P = 0.554), smoking (P = 0.428), preoperative serum creatinine >2 mg% (P = 0.785), history of cerebrovascular accident (P = 0.545), preoperative statin intake (P = 0.433), preoperative β-blockade (P = 0.151), and perioperative β-blockade (P = 0.297) did not significantly influence MACEs.
Multivariable Logistic Regression Analysis Using PP ≥80 mm Hg as a Predictor
Based on the univariate analyses described above, age, diabetes mellitus, history of MI, and PP ≥80 mm Hg were entered into a final logistic regression model. In the final model, only age was independently associated with MACEs (odds ratio, 1.06 for every year increase in age; 95% confidence interval, 1.02–1.10; P = 0.02). A PP ≥80 mm Hg was not associated with MACEs (odds ratio, 1.36; 95% confidence interval, 0.62–2.90; P = 0.44). There was no interaction between age and PP in the final multivariable logistic regression model.
Our study showed that preoperative PP is not a predictor of perioperative MACEs in patients having lower limb revascularization surgery. A secondary finding of this study was that preoperative PP is significantly higher in diabetics with peripheral vascular disease (PVD) undergoing lower extremity bypass surgery.
Our finding of no relationship between increased PP and outcomes after lower extremity revascularization surgery is in contrast to the findings from patients undergoing CABG, in which PP has been shown to be a predictor of both postoperative outcome10 and long-term survival.11 Atherosclerosis leads to both coronary artery disease and PVD. However, in our patients with PVD, PPs were uniformly increased >40 mm Hg with a closer spread (median [IQR] of 70 [57, 85] mm Hg). Thus, this uniform increase in PP might not be discriminatory enough to predict MACEs after lower extremity bypass surgery. Tseng21 demonstrated that PP increases steadily and significantly when patients progress from absence of PVD to mild PVD to severe PVD. Because patients who undergo lower extremity revascularization surgery have, by definition, severe PVD, they are likely to also have developed a high PP.
Previous studies10,22 showed a strong association between PP and postoperative stroke after cardiac surgery. However, none of the patients in our study had postoperative stroke. The hemodynamic fluctuations that can influence such outcomes observed in CABG surgery are much greater than those observed in patients undergoing lower extremity bypass surgery. Patients undergoing lower extremity revascularization surgery are not exposed to the same stroke risks as those undergoing CABG surgery, such as aortic manipulations of the ascending aorta (i.e., cross-clamping) or the use of cardiopulmonary bypass. If increased PP represents a reduced tolerance of the cerebrovascular system to these perturbations, the stresses of peripheral vascular surgery may not reach the threshold for causing stroke compared with CABG surgery. Therefore, PP may not have comparable prediction ability for MACEs in all types of surgery.
High PP is believed to be a manifestation of age- and disease-related stiffening of the central vasculature. In addition to reducing the compliance of the central vessels, the stiff vasculature causes an increase in the velocity of both the transmitted and the reflected pressure waves. Because of this increase in velocity, the reflected wave returns to the central circulation earlier than normal, during systole, thereby augmenting the systolic blood pressure and, by its absence, decreasing diastolic blood pressure.23 Arterial stiffness as measured by pulse wave velocity can vary in the central and peripheral arterial system. Various risk factors such as age and type 2 diabetes mellitus24 can affect central arteries more than the peripheral arteries. In contrast, the effect of sex hormones25 and statins26 on vascular stiffness are more pronounced on the peripheral arteries. Therefore, arterial stiffening is a heterogeneous condition and does not change uniformly throughout the arterial system.27–29 In fact, patients with lower extremity peripheral arterial disease have been shown to have reduced pulse wave velocity in the leg arteries.30 Differences in the pathogenesis and distribution of vascular stiffening of various forms of atherosclerosis such as coronary artery disease, peripheral artery disease, and cerebrovascular disease could help explain why, in contrast to the findings from CABG studies, we found no relation between increased PP and MACEs.10,22,27
Age was a significant predictor of MACEs after vascular surgery in our analysis, similar to other studies.31,32 In addition, a majority of our patients were diabetics (64%) and they had a higher PP in our cohort (40% of diabetics had PP ≥80 mm Hg, whereas 29% of the nondiabetic group had PP ≥80 mm Hg; P = 0.031). Type 2 diabetes has been related to preferential central arterial stiffness, which can result in higher PP.24 However, we did not see a relationship between diabetes and postoperative MACEs in our univariate analysis. There is conflicting evidence regarding the association of diabetes mellitus with MACEs in noncardiac surgery.33–36 We had shown earlier that, in our surgical population of 900 major vascular amputations, perioperative major adverse events were similar between diabetics and nondiabetics.37 This finding was attributed to aggressive perioperative and long-term management of the diabetic patients because of a close liaison with a major diabetes center.
The results of this study could have been attributable to a type II error. Another limitation is the retrospective nature of the study; the ability to obtain all 3 distinct preoperative blood pressures from the medical record was possible in only 65% of the patients. It is possible that the PP measure at the preoperative anesthetic visit immediately before surgery is not representative of a patient's true baseline pressures.
In conclusion, PP is not a significant predictor of perioperative MACEs in patients undergoing lower extremity revascularization surgery. Patients with severe PVD may have uniformly increased PP that may limit the discriminatory power to identify risk for MACEs after lower extremity bypass surgery.
Name: Amit Asopa, MD, FRCA.
Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.
Attestation: Amit Asopa has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Srinivas Jidge, MBBS.
Contribution: This author helped conduct the study.
Attestation: Srinivas Jidge has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Marc L. Schermerhorn, MD.
Contribution: This author helped analyze the data and write the manuscript.
Attestation: Marc L. Schermerhorn has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Philip E. Hess, MD, PhD.
Contribution: This author helped analyze the data and write the manuscript.
Attestation: Philip E. Hess has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Robina Matyal, MBBS.
Contribution: This author helped conduct the study and write the manuscript.
Attestation: Robina Matyal has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Balachundhar Subramaniam, MD, MPH.
Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.
Attestation: Balachundhar Subramaniam has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.
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