Association of chronic self-perceived stress with mortality and health status outcomes in patients with peripheral artery disease: insights from the portrait registry

Abstract

The prevalence of peripheral artery disease (PAD) is increasing worldwide and is estimated to affect about 360 million patients by 2030. Patients with PAD are at a higher risk of premature mortality and suffer from disability and functional impairment, both of which contribute to the direct and indirect socioeconomic burden of PAD. These trends are occurring despite emphasis towards control of traditional risk factors and interventions to decrease the impact of PAD on patient outcomes. Hence it is critical to identify and study novel risk factors that could impact outcomes in patients with PAD. Chronic mental stress could be one such factor. Mental stress is a potent cardiovascular risk factor and has been associated with development and progression of coronary disease and worse outcomes, including higher risk of mortality and poorer quality of life in patients after a myocardial infarction. However, there is paucity of evidence for the association of chronic mental stress with outcomes in PAD. To address this critical gap in understanding the link between mental stress and outcomes in PAD, we used data from the Patient-centered Outcomes Related to Treatment practices in peripheral Arterial disease: Investigating Trajectories (PORTRAIT), an international registry of patients presenting with symptoms of PAD. Mental stress was quantified at baseline, 3-, 6- and 12-month follow-up using the validated 4-item Perceived Stress Scale (PSS-4). For each patient available PSS-4 scores from all time points were averaged to quantify a subject’s average exposure to mental stress over one year. To examine the association of chronic stress with longitudinal mortality and health status outcomes, we did two separate landmark analysis. First to examine the impact of chronic stress on mortality we did a landmark analysis starting at 12-month follow-up. For each patient we defined chronic stress to be average of PSS-4 score at baseline through 12-months. Cox regression models adjusting for patients’ demographics (age, sex, race), comorbid conditions (diabetes, hypertension, history of myocardial infarction, congestive heart failure, smoking status), baseline ankle-brachial index, invasive treatment for PAD, socioeconomic indicators (highest education level, avoidance of care due to cost and end of the month resources), were used to assess an independent association of average stress (over first year of follow-up) with all-cause mortality over the subsequent four years. Second, to examine the association of chronic stress with 12-month health status outcomes we defined chronic stress exposure to be average PSS-4 score across baseline, 3- and 6-month follow-up assessments. This quantified a patient’s exposure to chronic stress over first 6-months of follow-up. Health status was quantified at baseline and 12-months. PAD specific health status was assessed using the PAD Questionnaire (PAQ). Generic health status was assessed using the EuroQoL Visual Analog Scale (EQ5D VAS). Hierarchical multivariable regression models, with random effects for site and adjustment for country, patients’ demographics, comorbid conditions, baseline ABI, treatment strategy and socioeconomic status-were used to examine independent association of average stress (baseline to 6-months) on recovery in health status at 12-months. In in patients in whom accurate assessment of chronic mental stress and mortality could be made (n=757, mean age 68.5 ± 9.7, 42% females, 28% non-Caucasians), higher average stress scores over 12-months were associated with greater hazards of mortality, in the adjusted model (hazard ratio per +1 unit increase in average PSS-4 1.08, 95% CI 1.01, 1.16 p=0.03). Similarly, in patients who had complete assessment of chronic stress over 6-months and health status at baseline and 12-month follow-up (n=1060, mean age 67.7, 37% females, 17.7% non-Caucasian) higher averaged stress scores over 6-months were associated with poorer PAQ summary score at 12-months in completely adjusted models (-1.4 points per +1-point increase in average PSS-4 95% CI -2.1, -0.6 p <0.001). Chronic stress in patients with PAD, is independently associated with higher mortality risk and poorer health status outcomes. These results set the stage for exploring interventions to examine if strategies to reduce chronic stress in patients with PAD improves outcomes