Pulse Pressure as a Risk Factor for Cardiovascular Events: Myth or Reality?

Research Article

Austin J Clin Cardiolog. 2019; 5(1): 1061.

Pulse Pressure as a Risk Factor for Cardiovascular Events: Myth or Reality?

Braite MS1*, Santos MA1, Wilson PG1, França JCQ1, Carvalho IG1 and Godoy MF

¹Department of Hemodynamics and Interventional Cardiology Service, Regional Medical School, Brazil

²Department of Cardiology and Cardiovascular Surgery, Sao Jose do Rio Preto Medical School, Brazil

*Corresponding author: Braite MS, Department of Hemodynamics and Interventional Cardiology Service, Regional Medical School - Funfarme, Rua Gastão Vidigal, Cruzeiro do Oeste, Brazil

Received: March 12, 2019; Accepted: May 22, 2019; Published: May 29, 2019

Abstract

Increased SBP and/or decreased DBP leads to an increase in systolic load, concomitant with a decrease in coronary perfusion pressure. Previous research has suggested a relationship between increases in PP and morbidity / mortality due to cardiovascular events.

Objective: This study aimed to demonstrate whether pulse pressure is in fact a predisposing factor for coronary heart disease and / or an aggravating risk in patients with CAD.

Methods: A total of 5,027 exams were studied. Of these, 3,052 (60.7%) were males. Age ranged from 20 to 92 years (59.0 {plus minus} 11.0 years). PP was determined invasively in the ascending aorta. Coronary artery disease was diagnosed if at least one of the major branches had obstructive lesion with a reduction of 50% or more in the diameter of its lumen. Statistical analyzes were performed with unpaired t-test or Mann-Whitney test for intergroup comparisons, as indicated. Categorical variables were compared using the chi-square test. Long-term survival was assessed using Kaplan-Meier curves. Values of P less than or equal to 0.05 were considered statistically significant.

Results: Pulse pressure varied from 20.0 to 160.0 mmHg, with a mean and standard deviation of 68.4 {plus minus} 22.3 (median of 66.0mmHg, 75th percentile of 82mmHg).

Conclusion: pulse pressure was not shown to be a risk factor for coronary heart disease in the comparison between patients with and without obstructive coronary disease. In addition, it was not independently relevant in the group with CAD patients with more advanced degrees of coronary disease and the pulse pressure showed no association with the patients age, being the only relevant independent variable. In other words, the influence of wrist pressure has confirmed to be a myth!

Keywords: Pulse pressure; Cardiovascular events; Atherosclerotic disease

Introduction

Pulse Pressure (PP) is the difference between Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) and it may be elevated due to increased SBP and decreased DBP [1].

Increased SBP and decreased DBP lead to elevated systolic load, concomitantly with decreased coronary perfusion pressure [2]. Importantly, increases in SBP cause a disproportionate increase in the end-systolic stress, which is the major hemodynamic factor that promotes cardiac hypertrophy, increased ventricular oxygen consumption and Left Ventricular (LV) hypertrophy, strongly compromising coronary perfusion.

Prior researches have suggested a relationship between increases in PP and morbidity/mortality due to cardiovascular events, which would even have a physiopathological explanation for Coronary Artery Diseases (CAD), based on the arguments described above [2- 6].

However, although cross-sectional analyses usually support the hypothesis that widened pulse pressure is an independent risk factor for cardiovascular diseases in general and more specifically CAD, prospective analyzes do not confirm this hypothesis [7].

Thus, based on a considerably large population and longer follow-up periods, this study aimed to demonstrate if pulse pressure is in fact a predisposing factor for coronary artery diseases and/or an aggravating risk in CAD patients, or if it fails to have an impact on the disease. Therefore, this is an existing conflict between Myth and Reality.

Methods

The examinations of 12,997 consecutive patients who underwent cardiac catheterization in the Hemodynamic Service of a University Hospital were assessed. Patients with valvopathy, congenital heart diseases, heart transplantation, hemodynamic instability or those who had already undergone myocardial revascularization procedures were excluded. Hence, a total of 5,027 examinations were used in the present study.

Of this total, 3,052 (60.7%) were males. Age ranged from 20 to 92 years (59.0 ± 11.0 years). PP was determined in an invasive manner by the absolute difference between the systolic and diastolic pressures in the ascending aorta at the beginning of the hemodynamic study. Coronary artery disease was diagnosed if at least one of the main branches (right coronary artery, interventricular anterior artery or diagonal artery, circumflex artery or left marginal artery) or Left Main Coronary Artery (LMCA) showed obstructive injury with a reduction of 50% or more in diameter of its light. The obstructive injury was considered advanced when at least 3 of the main branches, associated or not with the concomitant obstructive injury in the left main coronary artery, were involved.

Cut-off values for pulse pressure as a risk factor were established based on the median and 75% percentile of the selected sample. The digital records of each patient were analyzed prospectively, and death event was selected for analysis. To evaluate long-term mortality, 3 cut-off ranges were empirically established: pulse pressure greater than 40.0mmHg, pulse pressure greater than 60.0mmHg, and pulse pressure greater than 80.0mmHg. The statistical analyses were performed with unpaired t-test or Mann-Whitney test for the intergroup comparisons, depending on the Gaussian distribution or not of the variables. Categorical variables were compared using the Chi-Square test. Long-term survival was assessed using Kaplan-Meier curves. P values less than or equal to 0.05 were considered statistically significant.

Results

Pulse pressure ranged from 20.0 to 160.0 mmHg, with mean and standard deviation of 68.4 ± 22.3 (median of 66.0mmHg, 75th percentile of 82mmHg). Considering the median as a cut-off point, there were 2,453 (48.8%) patients with pulse pressure above that value. Of these, 1,481 had at least 1 major vessel with =50% obstruction. On the other hand, of the 2,574 patients with pulse pressure up to 66mmHg, 1,549 had obstructive CAD. The Chi-square analysis revealed P=0.9047 (OR = 1.00, 95% CI = 0.900 to 1.128).

The advanced degree of obstructive impairment was used as an analysis criterion. In the group with pulse pressure above median level, 411 patients showed tri-arterial impairment and 27 of them had compromised left main coronary artery. In the group with pulse pressure up to the median value, 368 patients presented with tri-arterial impairment and 20 of them had impaired left main coronary artery. The Chi-square statistical test compared tri-arterial impairment versus no obstruction and revealed P=0.053 (therefore not significant), with OR of 1.18 (95% CI 0.998 to 1.390).

Considering 75th percentile value (82mm Hg) as cut-off point, there were 1,217 (24.2%) patients with pulse pressure above that value. Of these, 750 had at least 1 major vessel with =50% obstruction. On the other hand, of the 3,810 patients with pulse pressure up to 82mmHg, 2280 had obstructive CAD. The Chi-square analysis revealed P=0.2829 (OR 1.08, 95% CI 0.944 to 1.230).

Using the advanced degree of obstructive impairment, the group with pulse pressure above the 75th percentile showed 208 patients with tri-arterial impairment, and 8 of them also had compromised left main coronary artery. In the group with pulse pressure below the 75th percentile, there were 571 patients with tri-arterial impairment, and 39 of them also had compromised left main coronary artery. Statistical analysis using the Chi-square test compared tri-arterial impairment and no obstruction and yielded P=0.075, OR of 1.19 and 95% CI 0.987 to 1.442). Thus, the analysis of significant numbers of cases (5,027) gives evidence that the elevated pulse pressure was not statistically more frequent in patients with obstructive coronary artery diseases than in non-coronary artery diseases, even when comparing a subgroup with advanced and normal coronary impairment.

Since pulse pressure was not confirmed as a risk marker for the incidence of coronary artery diseases, there was an attempt to verify whether pulse pressure exerted some effect related to the prognosis of the disease within a subgroup of CAD patients. According to the theory, the higher oxygen consumption due to a greater systolic work and due to the lower supply of oxygen in diastole would be logical pathophysiological mechanisms of greater myocardial damage. 922 patients with at least one compromised major branch (loss of vessel diameter greater than 50%) were prospectively evaluated. These patients were followed up during up to 225 months (mean, 142.7 ± 35.2 months, median 140 months). Comparisons were made based on different cut-off values.

The group with pulse pressure greater than 40mmHg included 821 patients, with 112 deaths. In the group of 101 patients with pulse pressure of 40mmHg or less, 11 deaths were observed (Hazard Ratio 1.134239, 95% CI 0.575462 to 2.233591, P=0.73). Survival at the end of follow-up in the group with pulse pressure greater than 40mmHg was 69.5 ± 5.6%; whereas survival was 81.3 ± 7.3% in the group with pulse pressure of 40mmHg or less.

The group with pulse pressure greater than 60mmHg comprised 488 patients, with 61 deaths. The group of 434 patients with pulse pressure of 60mmHg or less showed 62 deaths (Hazard Ratio 0.989931; 95% IC0.696182 to1.407626; P=0.955). Survival at the end of follow-up in the group with pulse pressure greater than 60mmHg was 75.4 ± 5.2%; and yet 68.6 ± 7.3% in the group with pulse pressure of 60mmHg or less.

The group with pulse pressure greater than 80 mmHg consisted of 220 patients with 27 deaths. In the group of 702 patients with pulse pressure of 80mmHg or less, 96 deaths could be observed (Hazard Ratio 1.109008; 95% CI 0.718917 to1.710764; P=0.629). Survival at the end of follow-up in the group with pulse pressure greater than 80mmHg was 80.9 ± 3.5%, and 69.6 ± 6.0 in the group with pulse pressure of 80mmHg or less. (Figures 1-3) illustrate death-free survival with Kaplan-Meier curves.