Pulse Pressure as a Marker of Prognosis in Acute Coronary Syndrome

Pulse pressure (PP) is the difference between the systolic (SBP) and the diastolic (DBP) blood pressure, which are dependent on the compliance of the aorta and large arteries and of the cardiac output1,2. Still, no circulation model explains this value separately2. Being easily evaluated at the hospital admission, PP has been found as predictor of the prognosis of cardiovascular events, more important than SBP and DBP separately. Likewise, there is evidence of this value being predictor of the risk of coronary artery disease (CAD)1,3-5. Both SBP and DBP increase in parallel to the age up to around 60 years, when SBP starts increasing and DBP, decreasing. This phenomenon results in a significant increase of PP after the 60 years. In elderly individuals, PP may be the key value for evaluating blood pressure, being important as risk factor for cardiovascular disease1,3,6.


Introduction
Pulse pressure (PP) is the difference between the systolic (SBP) and the diastolic (DBP) blood pressure, which are dependent on the compliance of the aorta and large arteries and of the cardiac output1,2.Still, no circulation model explains this value separately 2 .Being easily evaluated at the hospital admission, PP has been found as predictor of the prognosis of cardiovascular events, more important than SBP and DBP separately.Likewise, there is evidence of this value being predictor of the risk of coronary artery disease (CAD) 1,[3][4][5] .
Both SBP and DBP increase in parallel to the age up to around 60 years, when SBP starts increasing and DBP, decreasing.This phenomenon results in a significant increase of PP after the 60 years.In elderly individuals, PP may be the key value for evaluating blood pressure, being important as risk factor for cardiovascular disease 1,3,6 .
However, most of those evidences results from studies evaluating the impact of PP in non-acute cardiovascular situations, and the evaluations of the prognosis at the admission of the acute coronary events are rarer 7,8 .
The objective of this study was assessing the relation between the value of PP at the hospital admission and the risk of intra-hospital adverse events, and the seriousness of CAD in patients with acute coronary syndrome.

Methods
The study featured 8152 patients, included in the Portuguese National Record of ACS, consecutively admitted in coronary intensive care units with the diagnosis of ACS, between October 2010 and September 2013.The Record is approved and authorized by the National Committee of Data Protection under no.3140/2010.ACS comprises the acute ST segment elevation myocardial infarction (STEMI), defined as the presence of angina pectoris associated to new ST segment elevation (≥0.1 mV in all leads, to beyond V2-V3, in which the elevation must be ≥0.2 mV in men ≥40 years and ≥0.25 mV when <40 years or ≥0.15 mV in women), in at least two contiguous leads in the electrocardiogram (ECG); the acute non-ST segment elevation myocardial infarction (NSTEMI), characterized by the presence of angina pectoris associated to the ascending and/or descending curve of myocardial necrosis biomarkers (troponin I), with or without new ventricular repolarization changes suggesting myocardial ischemia in the ECG (ST segment depression and/or changes in the T waves) or new echocardiograph changes in the segmental contractility; unstable angina (UA), with the presence of angina pectoris, without elevation of myocardial necrosis biomarkers (troponin I); and the acute myocardial infarction of undetermined source (AMI US), characterized by angina pectoris, elevation and/or depression of troponin I, left bundle branch block (LBBB) and pacemaker rhythm in the ECG, with or without new changes in the segmental contractility.
The study did not include the patients that have not been through evaluation or had no information on the blood pressure at the hospital admission.The percutaneous therapy instituted was evaluated as well.
Regarding the laboratory variables, the values registered at the admission were of hemoglobin, serum creatinine, blood glucose, platelets, B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT pro-BNP) and LDL cholesterol.
Primary adverse events were defined as the intra-hospital occurrence of the death or reinfarction combination and the death, reinfarction, bleeding or HF combination.
Secondary adverse events were: the separate occurrence of death or bleeding (defined as decrease of Hb ≥5 g/dL, need for transfusion of erythrocyte concentrate or bleeding witnessed during the admission) or HF (defined as Killip-Kimbal class ≥2, LVEF <50%, BNP ≥500 pg/mL or NT pro-BNP ≥1800 pg/mL).The number of coronary arteries with disease and the involvement of the left main (LM) in the coronary angiography were considered as well.
The population studied was divided into two groups according to a cut-off PP value from which the presence of intra-hospital adverse events already mentioned is more significant (Group 1 = PP > cut-off and Group 2 = PP < cut-off).This value was achieved through the area under the ROC curve.
Both groups were relatively compared to the clinic, laboratory, and echocardiographic variables and to the percentage of adverse events and seriousness and extension of the coronary disease.
The continuous variables were expressed as mean+standard deviation and compared by using the one-way ANOVA and the Student's t tests.Categorical variables were expressed as frequencies and percentages and compared by using the chi-square test.The results with value p<0.05 were considered as statistically significant.
For evaluating the relation between PP value and the occurrence of the adverse events, predictors were determined, by using the logistic regression model.The model included the variables presenting differences statistically significant in the univariate analysis, with value p<0.05.1).
There is no statistically significant difference in the percentage of patients subject to the invasive therapeutic approach in both groups (87.4% vs. 88.3%, p=ns).In the STEMI patients, the onset-to-balloon time was longer for the patients with higher PP (258 min vs. 240 min; p=0.013), but the percentage of reperfused patients was similar in the two groups (85.8% vs. 87.9%,p=ns).90.4% was through primary angioplasty and 9.6%, fibrinolysis.
In the other ACS patients, no statistically significant difference was found for the time until the performance of the coronary angiography in any of the two groups.
No statistically significant difference was found in the laboratory values evaluated in both groups (Table 1).
PP value <50 mmHg was independent predictor of HF (OR 1.3 CI95% 1.1-1.4)and of the combination of events (OR 1.2 CI95% 1.1-1.4).In addition, these events had as independent predictors the renal failure and the GRACE score (Table 3).
Regarding the seriousness and extension of the coronary disease, the patients with higher PP values presented multiarterial disease more often (56.1% vs. 51.9%;p<0.001), with no statistically significant difference compared to the involvement of LM (7.8% vs. 7.2%; p=0.387) and to the simultaneous impairment of the three vessels (16.3% vs. 14.6%;p=0.076).risk of CAD, to the contrary of previously thought.An increase of the PP for a fixed SBP was related to an increased risk of CAD, rather than an increase of SBP for a fixed PP.
In respect to the PP relation to the seriousness and extension of CAD, not much information is found in the literature, and this study found more multiarterial disease for a higher PP, with no difference of the rate of LM involvement and the three vessels disease.One cannot determine yet whether PP is only a plain marker of vascular disease 1 .
The fact of PP being easily calculated with data mandatorily assessed at the hospital admission (SBP─DBP) makes it friendly, without additional costs.This may enable its systematic utilization as prognosis predictor in ACS in the future.
Other studies are required for the best comprehension of its relation to an increase in the number of intrahospital adverse events with ACS patients.
This study presents as limitations the fact of being based on a record, with all the obliquities inherent to it.Although it is a national record, the participation is of volunteers, and not all centers are participating or all patients are referenced.Despite being an appreciable sample volume, some data cannot be statistically valued, which may require a larger sample.The format of the National Record of ACS (NRACS) generates also a limitation at some points, the characteristics of adverse events not being completely explicit, which include a great variety of patients and clinic situations.This is the case of mortality, whose cause is not described.The troponin value cannot be attained through the National Record, which would have represented a significant utility in this study.

Conclusions
In this population of patients with ACS, despite the higher PP values being significantly related to worst cardiovascular risk profile, comorbidities and multiarterial disease in the coronary angiography, lower PP values were more associated to intra-hospital adverse events, being a PP<50 mmHg an independent predictor of those events.
The agility with which this value is attained at the hospital admission, without any additional cost, may enable its future application in the clinical practice.

Potential Conflicts of Interest
This study has no relevant conflicts of interest.

Sources of Funding
This study had no external funding sources.

Academic Association
This study is not associated with any graduate programs.
The following clinic variables were studied: SBP and DBP at the hospital admission, determining the difference between them, sourcing PP; age; sex; body mass index (BMI) and heart rate (HR) at the admission.The risk factors for cardiovascular disease (dyslipidemia, hypertension, diabetes mellitus and smoking), the presence of history of coronary disease (AMI and percutaneous or surgical coronary bypass grafting), cerebrovascular disease, peripheral artery disease, renal failure, cancer and chronic obstructive pulmonary disease (COPD) were determined.The development and seriousness of ACS were evaluated through the Killip-Kimbal class and GRACE score at the admission and the cardiac rhythm in the first ECG.

Figure 1 Figure 2
Figure 1Pulse pressure under the Killip-Kimbal class ns -non-significant

Table 1 Demographic, clinic and laboratory variables according to the pulse pressure value
BMI -body mass index; AMI -acute myocardial infarction; HF -heart failure; COPD -chronic obstructive pulmonary disease; PP -pulse pressure; SBP -systolic blood pressure; DBP -diastolic blood pressure; HR -heart rate; LVEF -left ventricular ejection fraction; BNP -B-type natriuretic peptide; NT Pro-BNP -N-terminal Pro-BNP; STEMI -acute ST segment elevation myocardial infarction; NSTEMI -acute non-ST segment elevation myocardial infarction; US -undetermined source; SD -standard deviation

Table 2 Intra-hospital adverse events according to the pulse pressure value
*Combination of events PP -pulse pressure