Firth, Christine

Abstract Context Peripheral artery disease (PAD) is highly prevalent in the general population, affecting up to 25% of patients 55 years of age or older. There is a known association with acute ischemic stroke, but limited large cohort studies exist pertaining to the relationship between PAD severity and incident ischemic stroke. Objectives To evaluate the risk of incident ischemic stroke and mortality along the spectrum of low and elevated ankle brachial index (ABI) measurement. Methods We performed a retrospective extraction of ABI data of all adult patients who underwent lower extremity physiology study for any indication from January 1, 1996 to June 30, 2018 in the Mayo Clinic health system. PAD was categorized into severe, moderate, mild, and borderline based on ABI measurements and poorly compressible arteries (PCA). These were compared with normal ABI measurements. Associations of PAD/PCA with new ischemic stroke events and all cause mortality were analyzed. Hazard ratios (HR) were calculated using multivariable Cox proportional regression with 95% confidence intervals. Results A total of 39,834 unique patients were included with a median follow up duration of 4.59 years. All abnormal ABI groups, except borderline PAD, were associated with increased risk of incident ischemic stroke after multivariate regression compared to normal ABI. A severity-dependent association was observed between PAD and ischemic stroke with moderate (HR, 1.22 [95% CI, 1.10–1.35]) and severe (HR, 1.19 [95% CI, 1.02–1.40]) categories conferring similar risk in comparison to normal ABI. Patients with PCA carried the greatest ischemic stroke risk (HR, 1.30 [95% CI, 1.15–1.46]). Similarly, abnormal ABI groups were associated with a significant risk for all cause mortality in a severity-dependent manner, with severe PAD conferring the greatest risk (HR, 3.07 [95% CI, 2.88–3.27]). Conclusions This study adds to the growing body of evidence that both PAD and PCA are independent risk factors for incident ischemic stroke and all cause mortality. The association of PAD severity and PCA with risk of ischemic stroke may help clinicians with risk stratification and determining treatment intensity.

Background Ankle‐brachial indexes ( ABI ) are a noninvasive diagnostic tool for peripheral arterial disease and a marker of increased cardiovascular risk. ABI is calculated using the highest systolic blood pressure of the 4 ankle arteries (bilateral dorsalis pedis and posterior tibial). Accordingly, patients may be assigned a normal ABI when the result would be abnormal if calculated using one of the other blood pressure readings. Cardiovascular outcomes for patients with discordant ABI s are undescribed. Methods and Results We performed a retrospective study of patients who underwent ABI measurement for any indication between January 1996 and June 2018. Those with normal ABI s (1.00–1.39) were included. We compared patients with all 4 normal ABI s (calculated using all 4 ankle arteries; n=15 577, median age 64.0 years, 54.4% men) to those with discordant ABI s (at least 1 abnormal ABI ≤0.99; n=2095, median age 66.0 years, 47.8% men). The outcomes assessed were ischemic stroke, myocardial infarction, and all‐cause mortality. Compared with patients with concordant normal ABI s, patients with discordant ABI s were older; women; smoked; and had chronic kidney disease, coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease, hypertension, or prior stroke. Patients with discordant ABI s had a greater risk of myocardial infarction (hazard ratio [HR], 1.31; 95% CI, 1.10–1.56), ischemic stroke ( HR, 1.53; 95% CI, 1.37–1.72), and all‐cause mortality ( HR, 1.27; 95% CI, 1.16–1.39), including after adjustment for baseline comorbidities. Conclusions Discordant ABI results were associated with an increased risk of myocardial infarction, stroke, and all‐cause mortality in the studied population. Clinicians should examine ABI calculations using all 4 ankle arteries to better characterize a patient's cardiovascular risk.

Abstract Background Peripheral arterial disease is a marker of aggressive atherosclerosis. The ankle brachial index (ABI) is a simple and non-invasive tool to diagnose peripheral arterial disease (PAD). Patients with PAD are at increased risk for ischemic strokes and other cardiovascular diseases. Purpose To evaluate the association of abnormal ABI and poorly compressible vessels with ischemic stroke in a large patient cohort. Methods We analyzed lower extremity vascular studies of all patients with ABI measurements at a tertiary care hospital between January 1996 and August 2018. PAD is defined as ABI<1.0, and poorly or non-compressible (PC/NC) arteries as ABI>1.4 while ABI between 1.0–1.4 is normal. Association of these ABIs with new ischemic stroke events post ABI measurement were analyzed after adjusting for high risk confounders such as atrial fibrillation. Hazard ratios (HR) were calculated using multivariable Cox proportional regression with 95% confidence intervals. Results In total, 38,016 unique patients (mean age 66.1±14.8 years, female 42.3%) were included. Abnormal ABI was found to be more prevalent among elderly male patients compared to patients with normal ABI. In contrast to non-PAD patients, both PAD and PC/NC patients as defined by ABI had a statistically significant risk of ischemic stroke, with PAD conferring the greatest risk compared to PC/NC vessels. The data is summarized in Table 1. Table 1 Unadjusted HR p-value Adjusted HR p-value PAD vs. No PAD 2.77 (2.62, 2.92) <0.001 2.10 (1.98, 2.22) <0.001 PC/NC vs. No PAD 2.11 (1.95, 2.28) <0.001 1.38 (1.26, 1.51) <0.001 PAD vs. PC/NC 1.37 (1.28, 1.46) <0.001 1.37 (1.28, 1.48) <0.001 Adjusted and unadjusted hazard ratios with p-values. HR adjusted for age, sex, atrial fibrillation, ischemic stroke, transient ischemic attack, chronic heart failure, diabetes mellitus, hyperlipidemia, hypertension, and coronary artery disease. PAD = Peripheral artery disease and PC/NC = poorly compressible/non-compressible. Conclusion This study adds to the growing body of evidence that PAD and poorly-compressible vessels are independently associated with an increased risk of ischemic stroke. Given the associated risk of cerebrovascular disease, clinicians should aggressively treat to minimize risk factors in those with abnormal ABIs.

Abstract Introduction Lower extremity physiologic studies are an important non-invasive diagnostic tool in peripheral arterial disease (PAD). PAD and atrial fibrillation (AF) are associated with increased cardiovascular and all-cause mortality. Purpose To evaluate the association between PAD and new-onset AF and the risk of stroke. Methods We performed a study of all patients without AF undergoing ankle-brachial index (ABI) for any indication between January 1996 to June 2018. The ABI cut-off were as follows: abnormal ABI (0–0.99), normal ABI (1.00–1.39) and poor vessel compressibility (PC) (1.40+). Demographic, comorbidity, and outcome variables were extracted using the electronic medical record. Results Overall, 34,441 patients (mean age 66.8±14.3, 57.3% male, 88.2% white) were included in the study with a median follow-up of 7.2 years (interquartile range, 3.0–12.9 years). Multivariate Cox proportional hazard analysis showed increased risk of new-onset AF for male sex, older age, hypertension, coronary artery disease, cerebrovascular disease, chronic kidney disease stage III or greater, congestive heart failure, chronic obstructive pulmonary disease, and cancer (all p<0.0001). After adjustment, ABI results were significantly associated with new-onset AF, particularly poorly-compressible vessels (adjusted HR: 1.42 (1.30–1.55), p<0.0001) compared to abnormal ABI (adjusted HR: 1.12 (1.05–1.20), p=0.0012). Patients with atrial fibrillation were more likely to experience ischemic stroke (39.2% versus 16.1%, p<0.0001). Conclusion Abnormalities in ABI results, particularly poorly-compressible vessels, are independently associated with new-onset atrial fibrillation in a large ambulatory cohort. While the mechanism cannot be assessed, common inflammatory mechanisms and increased vascular stiffness may play an important role. Identification of AF in these at-risk patients may improve cardiovascular outcomes.

Mycobacterium avium intracellulare infection or colonization should be considered in the differential diagnosis of hypercalcemia, especially in immunocompromised individuals, in the appropriate clinical context.