Incidence, Characteristics, and Outcomes of Myocardial Infarction in Patients With Peripheral Artery Disease

Abstract

IMPORTANCE Patients with peripheral artery disease (PAD) are at high risk for myocardial infarction (MI).OBJECTIVE To characterize the incidence and types of MI in a PAD population, identify factors associated with MI, and determine the association of MI with cardiovascular mortality and acute limb ischemia. DESIGN, SETTING, AND PARTICIPANTSThe Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease (EUCLID) was a double-blind randomized clinical trial conducted at 811 sites in 28 countries that randomized 13 885 patients with symptomatic PAD to monotherapy with ticagrelor or clopidogrel. Participants had an ankle-brachial index (ABI) of 0.80 or less or previous lower extremity revascularization. Median follow-up was 30 months. For these analyses, patients were evaluated for MI occurrence during follow-up irrespective of treatment. Data were analyzed from June 2017 to September 2018. MAIN OUTCOMES AND MEASURESAn adjudication clinical events committee classified MI as type 1 (spontaneous), type 2 (secondary), type 3 (sudden cardiac death), type 4a (less than 48 hours after percutaneous coronary intervention), type 4b (definite stent thrombosis), or type 5 (less than 72 hours after coronary artery bypass graft). A multivariate regression model was developed by stepwise selection to identify factors associated with MI, and a time-dependent multivariate Cox regression analysis was performed to determine the association of MI with cardiovascular death and acute limb ischemia requiring hospitalization. RESULTSOf the 13 885 patients included in this analysis, 9997 (72.0%) were male, and the median (interquartile range) age was 66 (60-73) years. Myocardial infarction occurred in 683 patients (4.9%; 2.4 events per 100 patient-years) during a median follow-up of 30 months. Patients experiencing MI were older (median [interquartile range] age, 69 [62-75] vs 66 [60-72] years), more likely to have diabetes (349 of 683 [51.1%] vs 4996 of 13 202 [37.8%]) or a previous lower extremity revascularization (466 of 683 [68.2%] vs 7409 of 13 202 [56.1%]), and had a lower ABI (if included by ABI) compared with censored patients. Of the 683 patients with MI during follow-up, the most common MI type was type 1 (405 [59.3%]), followed by type 2 (236 [34.6%]), type 4a (14 [2.0%]), type 3 (12 [1.8%]), type 4b (11 [1.6%]), and type 5 (5 [0.7%]). Postrandomization MI was independently associated with cardiovascular death (adjusted hazard ratio, 9.0; 95% CI, 7.3-11.2; P < .001) and acute limb ischemia requiring hospitalization (adjusted hazard ratio, 2.5; 95% CI, 1.3-5.0; P = .008). CONCLUSIONS AND RELEVANCEApproximately 5% of patients with symptomatic PAD had an MI during a median follow-up of 30 months. Type 1 MI (spontaneous) was the most common MI type; however, one-third of MIs were type 2 MI (secondary). More research is needed to identify therapies to reduce the risk of MI in patients with PAD and to improve management of type 2 MI.

Diabetes mellitus and other cardiovascular risk factors in lower-extremity peripheral artery disease versus coronary artery disease: an analysis of 1,121,359 cases from the nationwide databases

“…Consequently, diabetes mellitus and other cardiovascular risk factors are commonly accumulated not only in CAD patients but also in LE-PAD patients. In addition, LE-PAD patients are at high risk of future coronary events [4], as are CAD patients. Such common features of the two cardiovascular diseases (CVDs) have been repeatedly emphasized when discussing the importance of cardiovascular risk management in an LE-PAD population [1, 2].…”

The association between serum growth differentiation factor 15 levels and lower extremity atherosclerotic disease is independent of body mass index in type 2 diabetes

“…LEAD is the manifestation of peripheral atherosclerotic disease and is characterized as the stenosis and occlusion of lower limb arteries [25]. Due to the similar pathophysiological mechanisms (such as oxidative stress and endothelial dysfunction) between LEAD and atherosclerosis in other vasculature, LEAD is closely related to the occurrence of cardiovascular disease [11,12,26]. In addition, diabetes-associated LEAD is often concomitant with neuropathy [27].…”

“…Lower extremity atherosclerotic disease (LEAD) is one of the major vascular complications of diabetes and is associated with a substantial increase in the risk of nonfatal (such as gangrene, amputation, etc.) and fatal cardio-and cerebrovascular events [11,12]. Furthermore, diabetes was observed to be independently associated with an increased risk of LEAD, depending on the severity of cardiovascular diseases [13].…”

Pathophysiology of Spontaneous Coronary Artery Dissection Determines Anticoagulation Strategy

“…In cases of multivessel disease, anti-inflammatory therapy may need to be escalated as described in the referenced articles [ 27 - 29 ]. Plasmapheresis, intravenous immune globulin, and steroids were necessary to reverse the fetal antigen-mediated multivessel immune-mediated coronary syndrome.…”