Association of pulse pressure with risk of major adverse cardiovascular events among cardiovascular outcome trial participants

Abstract

Abstract Background Hypertension is a well-established risk factor for the development for cardiovascular (CV) disease and accumulating evidence also implicates elevated pulse pressure (PP), a surrogate marker for arterial stiffness, as an independent risk factor for major adverse cardiovascular events (MACE). Purpose The study aimed to assess the association of PP with MACE among participants in multiple CV outcome clinical trials. It also aimed to determine if the presence of various CV comorbidities impacts the association between PP and MACE. Methods Adult patients between the ages of 19-98 years (n = 65,382, mean age 63) enrolled in five large CV outcome trials (ACCELERATE, STRENGTH, PRECISION, ALECARDIO, and LIGHT) with independently adjudicated clinical end points were identified. Baseline demographics, medical history, blood pressures, and CV medications were collected. Univariate and multivariate analyses were generated and analyzed for temporal trends, risk, and adjusted survival. Results Participants had a mean baseline blood pressure of 128 /76 mm Hg and a mean PP of 52 mm Hg. Forty-five percent were women, 31% had coronary artery disease, 51% had type 2 diabetes mellitus, 84% had hypertension, 25% had history of myocardial infarction (MI), and 35% had a history of an acute coronary syndrome. The composite MACE end point included CV death, myocardial infarction, or stroke and occurred in 3712 participants (5.7%).The composite end point of all cause death, myocardial infarction, and stroke occurred in 4513 participants (6.9%). For every 10 mm Hg increase in PP there was an increased risk of MACE (unadjusted hazard ratio (HR) 1.20, 95% CI 1.17 to 1.23). Similarly, a PP > 60 mmHg demonstrated an unadjusted HR of 1.53 (95% CI 1.43 to 1.64) compared with PP < 60 mm Hg. Although increased PP was a risk factor in both men and women, every 10 mm Hg increase in PP was associated with higher risk of MACE in women (adjusted HR 1.17, 95%CI 1.17, 1.12 to 1.22) compared with men (adjusted HR 1.09, 95% CI, 1.05 to 1.12). Table 1 displays the adjusted HR for patients grouped by race, history of prior CV disease, or the presence of CV risk factors (diabetes and chronic kidney disease.) While most subgroups demonstrated an increased risk of MACE with increasing PP, PP was not associated with MACE among individuals with a history of stroke (HR 1.00, 95% CI 0.92 to 1.08). Kaplan-Meier survival curves comparing PP greater than or less than 60 mm Hg are seen in Figure 1. Conclusions Among CV outcome clinical trial participants, with independently adjudicated end points, baseline PP is associated with an increased risk for future MACE. The association stands for most participant subgroups except for participants with a prior history of stroke.Table 1Figure 1