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BACKGROUND AND AIMS: Polyvascular disease is an independent predictor of major adverse cardiovascular events (MACE). The relationship between the number of diseased arterial beds and MACE is unknown. How MACE risk changes in individuals with type 2 diabetes (T2D) is also understudied. Furthermore, it is unknown whether heart failure (HF) status and hemoglobin A1c (HbA1c) levels influence outcomes in polyvascular disease. This analysis from the Exenatide Study of Cardiovascular Event Lowering trial (EXSCEL) aimed to examine the risk associated with increasing number of diseased arterial beds on MACE and all-cause mortality (ACM). METHODS: Cox models were used to test associations between the number of diseased arterial beds and MACE and ACM. Prespecified interaction testing between number of diseased arterial beds with baseline HF, HbA1c (≤8% vs. >8%), and treatment assignment was performed. RESULTS: Overall, 14,751 participants were included; 26.5% were without atherosclerosis, 58.9% had 1-bed, 12.3% had 2-bed, and 2.3% had 3-bed disease. An increasing burden of atherosclerotic disease was associated with increasing risk of MACE (adjusted HR [aHR] 1.71 [95% CI 1.46–2.02]; 2.61 [2.17–3.15]; 3.46 [2.69–4.45] for 1, 2, and 3 beds, respectively, p < 0.001 for all) and ACM (1.94 [1.56–2.42]; 3.03 [2.33–3.95]; 3.66 [2.59–5.18] for 1, 2, and 3 beds, respectively, p < 0.001 for all). Prespecified interaction testing did not reveal any significant associations. CONCLUSIONS: In patients with T2D, compared to those without atherosclerotic vascular disease, risk of MACE and ACM increases incrementally with each additional diseased arterial bed.

ImportanceReported risk of incident peripheral artery disease (PAD) by sex and race varies significantly and has not been reported in national cohorts among individuals free of baseline PAD.ObjectiveTo evaluate the association of sex and race, as well as prevalent cardiovascular risk factors, with limb outcomes in a national cohort of people with normal baseline ankle-brachial indices (ABIs).Design, setting, and participantsThis cohort study was conducted using data from participants in the Veterans Affairs Birth Cohort Study (born 1945-1965), with follow-up data between January 1, 2000, and December 31, 2016. Baseline demographics were collected from 77 041 participants receiving care from the Veterans Health Administration with baseline ABIs of 0.90 to 1.40 and no history of PAD. Data were analyzed from October 2019 through September 2022.ExposuresSex, race, diabetes, and smoking status.Main Outcomes and MeasuresIncident PAD, defined as subsequent ABI less than 0.90, surgical or percutaneous revascularization, or nontraumatic amputation.ResultsOf 77 041 participants with normal ABIs (73 822 [95.8%] men; mean [SD] age, 60.2 [5.9] years; 13 080 Black [18.2%] and 54 377 White [75.6%] among 71 911 participants with race and ethnicity data), there were 6692 incident PAD events over a median [IQR] of 3.9 [1.7-6.9] years. Incidence rates were lower for women than men (incidence rates [IRs] per 1000 person-years, 7.4 incidents [95% CI, 6.2-8.8 incidents] vs 19.2 incidents [95% CI, 18.7-19.6 incidents]), with a lower risk of incident PAD (adjusted hazard ratio [aHR], 0.49 [95% CI, 0.41-0.59]). IRs per 1000 person-years of incident PAD were similar for Black and White participants (18.9 incidents [95% CI, 17.9-20.1 incidents] vs 18.8 incidents [95% CI, 18.3-19.4]). Compared with White participants, Black participants had increased risk of total PAD (aHR, 1.09 [95% CI, 1.02-1.16]) and nontraumatic amputation (aHR, 1.20 [95% CI, 1.06-1.36]) but not surgical or percutaneous revascularization (aHR, 1.10 [95% CI, 0.98-1.23]) or subsequent ABI less than 0.90 (aHR, 1.04 [95% CI, 0.95-1.13]). Diabetes (aHR, 1.62 [95% CI, 1.53-1.72]) and smoking (eg, current vs never: aHR, 1.76 [95% CI, 1.64-1.89]) were associated with incident PAD. Incident PAD was rare among individuals without a history of smoking or diabetes (eg, among 632 women: IR per 1000 people-years, 2.1 incidents [95% CI, 1.0-4.5 incidents]) despite an otherwise–high-risk cardiovascular profile (eg, 527 women [83.4%] with hypertension).Conclusions and RelevanceThis study found that the risk of PAD was approximately 50% lower in women than men and less than 10% higher for Black vs White participants, while the risk of nontraumatic amputation was 20% higher among Black compared with White participants.

Atherosclerotic lower extremity peripheral artery disease (PAD) is increasingly recognized as an important cause of cardiovascular morbidity and mortality that affects >230 million people worldwide. Traditional cardiovascular risk factors, including advanced age, smoking, and diabetes, are strongly linked to an increase risk of PAD. Although PAD has been historically underappreciated compared with coronary artery disease and stroke, greater attention on PAD in recent years has led to important new epidemiological insights in the areas of thrombosis, inflammation, dyslipidemia, and microvascular disease. In addition, the concept of polyvascular disease, or clinically evident atherosclerosis in multiple arterial beds, is increasingly identified as a particularly malignant cardiovascular disease worthy of special clinical attention and further study. It is noteworthy that PAD may increase the risk of adverse outcomes in similar or even greater magnitude than coronary disease or stroke. In this review, we highlight important new advances in the epidemiology of PAD with a particular focus on polyvascular disease, emerging biomarkers, and differential risk pathways for PAD compared with other atherosclerotic diseases.

There is a lack of consistency among the ACC/AHA and ESC Guidelines on the treatment of patients with lower extremity PAD to a targeted LDL-c level. A review of the current guidelines, as well as the evidence that exists for use of various lipid-lower therapies in patients with PAD, is needed to guide clinical practice and to examine the current gaps in evidence that exist.There is evidence that statins and PCSK9 inhibitors reduce the risks of major adverse cardiovascular and limb events in patients with PAD. Most statin and non-statin trials have examined the association of LLT use with clinical outcomes, and not the association between the degree of LDL-c lowering and the reduction in risk of clinical outcomes. As such, there is a lack of agreement between the American and European PAD Guidelines over whether to treat patients with PAD to a targeted LDL-c goal. Both statins and PCSK9 inhibitors have been shown to reduce the risk of major cardiovascular and limb events in patients with PAD. Further research is needed to determine if target driven LDL-c lowering is associated with improved outcomes in patients with PAD.

Coronavirus disease of 2019 poses significant risks for patients with vascular disease. Telemedicine can help clinicians provide care for patients with vascular disease while adhering to social-distancing guidelines. In this article, we review the components of telemedicine used in the vascular medicine practice at the Vanderbilt University Medical Center. In addition, we describe inpatient and outpatient diagnosis-based algorithms to help select patients for telemedicine versus in-person evaluation.

Although the resting ankle–brachial index (ABI) is commonly used as a httptool to diagnose peripheral artery disease (PAD), several additional indices measured after exercise may have increased sensitivity for identifying PAD. The aim of this study was to determine the utility of resting ABI and three post-exercise physiological parameters for diagnosing PAD confirmed by arterial imaging studies. For each qualifying study, we assessed the performance measures for identifying PAD for resting ABI < 0.90, exercise ABI < 0.90, a decrease in ABI > 20% with exercise, and a decrease in ankle pressure > 30 mmHg with exercise. Of the 199 exams that met our inclusion criteria, imaging showed a > 75% stenotic lesion in at least one limb in 138 (69%) of patients. For stenoses > 75%, resting ABI < 0.90 had a sensitivity of 64% (95% CI: 56–72%) and exercise ABI < 0.90 had a sensitivity of 88% (95% CI: 82–93%). The sensitivity for a post-exercise ABI decrease > 20% was 67% (95% CI: 59–75%) and the sensitivity for a decrease in ankle pressure > 30 mmHg was 4% (95% CI: 2–9%). For individuals with a normal resting ABI but stenotic lesions > 75% confirmed by imaging (n=49), the addition of exercise ABI testing correctly identified an additional 25% of this population. Overall, exercise ABI < 0.90 exhibits a greater sensitivity for detecting PAD compared to resting ABI. Furthermore, exercise ABI < 0.90 had added clinical utility in patients with normal resting ABIs and was superior to other commonly used exercise indices.

Background: The combination of statin therapy and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition markedly lowers low-density lipoprotein cholesterol (LDL-C) and reduces cardiovascular event rates. Whether residual inflammatory risk as measured by on-treatment high sensitivity C-reactive protein (hsCRP) remains an important clinical issue in such patients is uncertain. Methods: We evaluated residual inflammatory risk among 9738 patients participating in the SPIRE-1 and SPIRE-2 cardiovascular outcomes trials (Studies of PCSK9 Inhibition and the Reduction in Vascular Events), who were receiving both statin therapy and bococizumab, according to on-treatment levels of hsCRP (hsCRP OT ) and LDL-C OT measured 14 weeks after drug initiation. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death. Results: At 14 weeks, the mean percentage change in LDL-C among statin-treated patients who additionally received bococizumab was −60.5% (95% confidence interval [CI], −61.2 to −59.8; P P =0.09; median change, 0.0%) for hsCRP. Incidence rates for future cardiovascular events for patients treated with both statin therapy and bococizumab according to hsCRP OT 3 mg/L were 1.96, 2.50, and 3.59 events per 100 person-years, respectively, corresponding to multivariable adjusted hazard ratios of 1.0, 1.16 (95% CI, 0.81–1.66), and 1.62 (95% CI, 1.14–2.30) ( P -trend=0.001) after adjustment for traditional cardiovascular risk factors and LDL-C OT . Comparable adjusted hazard ratios for LDL-C OT (50 mg/dL) were 1.0, 0.87, and 1.21, respectively ( P -trend=0.16). Relative risk reductions with bococizumab were similar across hsCRP OT groups ( P -interaction=0.87). Conclusions: In this post hoc analysis of the SPIRE trials of bococizumab in a stable outpatient population, evidence of residual inflammatory risk persisted among patients treated with both statin therapy and proprotein convertase subtilisin-kexin type 9 inhibition. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01975376, NCT01975389.

There are no large national cohorts examining the incidence of peripheral artery disease (PAD) among participants previously tested for PAD by ankle-brachial index (ABI) at baseline. Such data are critical as prevalent PAD often goes unrecognized. We analyzed 164,441 participants in the Veterans

Plasma biomarkers of cardiometabolic health are invaluable tools for cardiovascular disease (CVD) and type 2 diabetes (T2D) risk stratification. Data driven patient classification may offer unbiased insights into dominant biologic risk factors that determine avenues for risk reduction. We conducted

Numerous cross-sectional studies of venous thromboembolism (VTE) have identified plasma homocysteine as a potential risk factor for VTE. In contrast, prospective data are sparse with limited studies conducted among women. Given current interest in expanded indications for anticoagulation therapy, we

Background: Although the resting ankle-brachial index (ABI) is commonly used to diagnose peripheral artery disease (PAD), limited data suggest several indices measured after exercise may have increased sensitivity for identifying PAD. The aim of this study was to determine the utility of resting ABI