Aaron W. Aday

Introduction: Extracoronary vascular abnormalities (EVAs) are common in patients with spontaneous coronary artery dissection (SCAD), and expert consensus statements recommend evaluation with head-to-pelvis cross-sectional imaging. Lack of a universal imaging protocol remains a barrier to consistent implementation of this recommendation. We sought to implement a high-fidelity, single-session, head-to-pelvis computed tomography angiography (CTA) protocol that minimizes radiation and contrast exposure compared to multisession CTA. Methods: A total of 97 consecutive patients with SCAD were evaluated with a single-session CTA (SS-CTA protocol). The comparison group consisted of 63 consecutive patients who underwent asynchronous CTA of different body segments (MS-CTA). The primary outcome was total radiation dose and contrast volume in each imaging protocol. The secondary outcome was prevalence of EVAs. Results: There was no difference in baseline characteristics, SCAD presentation, or management between groups. The SS-CTA protocol had a 24% lower radiation dose (1873 ± 676 mGy-cm vs 2452 ± 1099 mGy-cm, p < 0.001) and a 21% lower contrast volume (161.2 ± 48.7 mL vs 203.8 ± 68.4 mL, p < 0.001) compared to the MS-CTA protocol. There was no significant difference in the prevalence of EVAs detected between imaging groups (55.7% vs 57.1%, p = 0.854). Conclusion: This study demonstrates the effectiveness of a single-acquisition CTA protocol for EVA detection in patients with SCAD. The SS-CTA protocol minimized radiation and contrast exposure for a patient population that may require frequent imaging over the lifespan. Further studies are needed to determine whether expanded availability of this protocol would improve adherence to expert consensus recommendations.

BACKGROUND: Patients with peripheral artery disease experience walking impairment that is incompletely explained by large-artery atherosclerotic occlusive disease and abnormal ankle-brachial index (ABI). Microvascular dysfunction is associated with adverse outcomes, including amputation, but its effect on ambulation is unknown. We tested the hypothesis that skeletal muscle microvascular function directly associates with walking distance, is a more sensitive indicator of walking distance than conduit artery blood inflow, and correlates with ambulatory improvement following peripheral artery disease interventions. METHODS: Sixty-eight participants, including 50 with peripheral artery disease (ABI ≤0.85) and 18 healthy controls, underwent vascular function assessment after sphygmomanometer cuff-induced calf ischemia using magnetic resonance imaging measures of blood oxygenation level–dependent reactivity and arterial spin labeling perfusion reactivity. Functional status was assessed using the 6-minute walk test. A subgroup of patients with peripheral artery disease underwent repeat testing after supervised exercise therapy (n=14) or revascularization (n=14). Multivariable linear regression models were used to assess the association of macrovascular reactive hyperemic blood inflow within the conduit arteries, skeletal muscle microvascular blood oxygenation level–dependent reactivity, and walking distance. RESULTS: Resting large-artery pressure by ABI (R=0.74; P P P P =0.023). In those with repeat testing after intervention, the change in microvascular reactivity, but not ABI or macrovascular blood inflow, significantly correlated with the change in the 6-minute walk test distance (R=0.46; P =0.014). CONCLUSIONS: Microvascular reactivity after ischemia directly associates with walking distance and was a stronger predictor of walking distance than macrovascular blood inflow and ABI. After supervised exercise therapy or revascularization, improvements in microvascular function, but not macrovascular inflow or ABI, correlate with improvement in walking distance. Further study of microvascular dysfunction as a mechanistic driver of ambulatory function is warranted. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03490968.

Background: Traditional cardiovascular risk assessment entails investigator‐defined exposure levels and individual risk markers in multivariable analysis. We sought to determine whether an alternative unbiased learning analysis might provide further insights into vascular risk. Methods: We conducted an unsupervised learning (k‐means cluster) analysis in the Women's Health Study (N=26 443) using baseline levels of triglycerides, high‐sensitivity C‐reactive protein, and low‐density lipoprotein cholesterol to form novel exposures. We then evaluated cluster‐based risk of incident coronary, cerebrovascular, and limb events using the Kaplan–Meier method and multivariable Cox models, followed by comparison with established clinical biomarker thresholds. Finally, we illustrated clinical applicability to a nonvascular outcome (type 2 diabetes). Results: Four clusters emerged and were named according to aggregate biomarker profiles: Cluster 1 (“healthy,” n=12 101), cluster 2 (“hypercholesterolemic,” n=7424), cluster 3 (“inflammatory,” n=5056), and cluster 4 (“triglyceride‐rich,” n=1862). Triglyceride‐rich cluster identity conferred the highest risk of future cardiovascular events (adjusted hazard ratio [HR _adj ], 2.24 [95% CI, 1.93–2.60]) compared with those in the healthy cluster (reference group). Risk was intermediate in the hypercholesterolemic (predominantly elevated low‐density lipoprotein cholesterol) and inflammatory (predominantly elevated high‐sensitivity C‐reactive protein) clusters (HR _adj , 1.44 [95% CI, 1.28–1.61]; and 1.54 [95% CI, 1.35–1.75], respectively). Clustering yielded stronger total cardiovascular disease risk associations than traditionally defined mixed dyslipidemia with modest improvement in reclassification statistics. Cluster identities also predicted incident type 2 diabetes, with the greatest risk among the triglyceride‐rich cluster (HR _adj , 3.78 [95% CI, 3.29–4.35]). Conclusions: Unsupervised learning analyses demonstrated associations that may be useful when refining cardiovascular risk and may inform atherosclerosis development in healthy individuals better than traditional classification methods. Registration: URL: https://clinicaltrials.gov ; Unique identifier: NCT00000479.

Background: The BEST‐CLI (Best Endovascular Versus Best Surgical Therapy in Patients With Critical Limb Ischemia) trial tested the optimal initial revascularization strategy in patients with chronic limb‐threatening ischemia. Little is known about the prognostic relevance of Lp(a) (lipoprotein[a]) and its modification by renal function in patients with chronic limb‐threatening ischemia. We investigated the relationship between Lp(a) and prespecified cardiovascular outcomes. Methods: A subgroup of patients from the BEST‐CLI trial (as part of the TIDE [The Impact of Diabetes on Revascularization] study) underwent blinded, core‐laboratory assessment of Lp(a) levels and were included in this analysis. The primary end point was major adverse limb events or death from any cause. Secondary end points were the components of the primary end point, major amputation, major reintervention, and major adverse cardiac events (myocardial infarction, ischemic stroke, or death from any cause). The association of Lp(a) with end points was assessed using Cox proportional hazard models adjusting for traditional risk factors and then also for renal function and statin use, which increase Lp(a) levels. Results: A total of 189 patients (median [interquartile range] age 67.3 [61.6–74.1] years) were included and followed for a median of 2.1 (1.2–2.9) years. Median Lp(a) for the total study population was 27.3 (10.4–65.8) mg/dL, and 62 (32.8%) patients had elevated values (≥50 mg/dL). The 1‐year event rate of the primary outcome was 33.3 (95% CI, 23.7–42.8) per 100 person‐years. There was no association between Lp(a) and the primary outcome (hazard ratio [HR], 1.00 [95% CI, 0.99–1.00]; P =0.186). In secondary analyses controlling for renal function, elevated Lp(a) was associated with increased risk for all‐cause death (HR, 1.03 [95% CI, 1.01–1.05]; P =0.009). Results were similar regardless of peripheral revascularization strategy. Conclusions: Elevated Lp(a) level was not associated with major adverse limb events or death but was associated with all‐cause death after controlling for renal function. Lp(a) may be an important therapeutic target in the patient population with high‐risk chronic limb‐threatening ischemia. Registration: https://clinicaltrials.gov/study/NCT03085524 ; Unique identifier: NCT03085524.