Reassessing Cardiovascular Risk in Patients with Peripheral Artery Disease undergoing Myocardial Perfusion Imaging.

Background: Coronary artery disease(CAD) and peripheral artery disease(PAD) are often regarded as analogous risk factors for major adverse cardiovascular events(MACE) given their shared pathophysiology. We aimed to investigate whether the elevated MACE risk in PAD is driven by myocardial perfusion abnormalities or through other PAD-specific mediators.

Methods: We analyzed 45252 patients from an international, multicenter registry who underwent SPECT myocardial perfusion imaging, excluding those with early coronary revascularization (<90 days). Myocardial perfusion abnormalities were quantified using total perfusion deficit (TPD). MACE was defined as all-cause mortality, unstable angina admission, myocardial infarction or late coronary revascularization. PAD was defined using questionnaires or review of electronic medical records. Propensity score matching was used to select balanced groups of patients with and without PAD.

Results: During a median follow-up of 3.6 years (IQR: 2.6 - 4.8 years), 5932 patients (13.7%) experienced at least one MACE. Compared to patients with neither disease, isolated history of CAD (aHR: 1.92, 95% CI: 1.80-2.05) conferred a similar MACE risk as concomitant history of CAD and PAD (aHR: 1.57, 95%CI: 1.44-1.71) and greater risk than isolated history of PAD (aHR: 1.20, 95%CI: 1.09-1.32, p<0.001). After propensity-score matching, history of PAD alone was not independently associated with increased MACE risk (p=0.064).

Conclusions: Although patients with PAD often have concomitant CAD and greater myocardial perfusion abnormalities, PAD itself was not linked to higher MACE risk after adjusting for these factors. These findings highlight the importance of assessing myocardial ischemic burden in PAD for risk-stratification and prompt initiation of disease-modifying therapies.