Cardiac Rehabilitation in Patients with Peripheral Artery Disease—A Literature Review in COVID-19 Era

Cardiac rehabilitation (CR) is an integral part of the management of various cardiovascular disease such as coronary artery disease (CAD), peripheral artery disease (PAD), or chronic heart failure (CHF), with proven morbidity and mortality benefits. This article aims to review and summarize the scientific literature related to cardiac rehabilitation programs for patients with PAD and how they were adapted during the COVID-19 pandemic. The implementation of CR programs has been problematic since the COVID-19 pandemic due to social distancing and work-related restrictions. One of the main challenges for physicians and health systems alike has been the management of PAD patients. COVID-19 predisposes to coagulation disorders that can lead to severe thrombotic events. Home-based walking exercises are more accessible and easier to accept than supervised exercise programs. Cycling or other forms of exercise are more entertaining or challenging alternatives to exercise therapy. Besides treadmill exercises, upper- and lower-extremity ergometry also has great functional benefits, especially regarding walking endurance. Supervised exercise therapy has a positive impact on both functional capacity and also on the quality of life of such patients. The most effective manner to acquire this seems to be by combining revascularization therapy and supervised exercise. Rehabilitation programs proved to be a mandatory part of the integrative approach in these cases, increasing quality of life, and decreasing stress levels, depression, and anxiety.

The association between ABO blood groups and TASC II classification in patients with peripheral artery disease

Objective The aim of this study was to investigate the association between blood groups and severity of peripheral artery disease (PAD) using TASC II classification. Methods The patients who were diagnosed with PAD were retrospectively analyzed. The patients with 50% or more stenosis in the aorto-iliac or femoro-popliteal region detected by conventional or CT angiography were included in the study. These patients were divided into TASC II A, B, C, and D groups considering the severity of PAD. All patients’ blood groups were recorded and compared between TASC II groups. Results While 38% of the study population was O blood group, 61% were non-O group. On the other hand, 90% of the entire study population were RH positive and 10% were RH negative. Non-O blood ratio was found to be significantly higher in patients with higher TASC II groups. (TASC IIA 51.6% vs. TASC IIB 57.9% vs. TASC IIC 61.3% vs. TASC IID 76.6%, p< .001) However, the frequencies of Rh types were similar in all groups. Multiple logistic regression analysis was applied for determining the predictors of severity and complexity of PAD (TASC II C and TASC II D lesions) Conclusions Our study results revealed a clear association between ABO blood groups and severity of peripheral arterial disease. Non-O blood group was found to be the independent predictor of severe and complex PAD.

Serum Uric Acid as a Predictor of cardio-and cerebro-vascular diseases in Maintenance Hemodialysis Patients

Background: Hyperuricemia is associated with an increased risk of cardio-and cerebrovascular disease (CVD) in general population. However, in the hemodialysis (HD) patients, low serum uric acid (SUA) increases the risk of mortality. Considering that CVD is the principal cause of death among maintenance HD patients, the present study aimed to determine the predictive value of SUA for CVD outcome in this population. Methods: In this two-year follow-up prospective study, 205 outpatients under maintenance HD were enrolled from March 2017 to 2020. Patients’ demographic data, underlying diseases, and the results of serum tests, as well as two-year follow-up results of CVD events and mortality were recorded. Results: A total of 130 (63%) patients were eligible for analysis; 62.9% were male; mean age of participants was 59±13years. At follow-up, coronary artery disease was observed in 43.2%, peripheral artery disease in 26.5%, and cerebrovascular disease in 20.5%; angiography was required in 52.3% and 4.5% died of CVD. SUA was ≤5.4 mg/dL in 52 patients, 5.5-6.1 mg/dL in 19, and ≥6.2 mg/dL in 59 patients with significant difference based on mean age, sex distribution, occurrence of cerebrovascular disease and cardiovascular mortality (P<0.05). Patients with cerebrovascular disease had a significantly lower SUA levels (P=0.006). Logistic regression showed the significant effect of SUA on the occurrence of cerebrovascular disease (P=0.008). Conclusion: Low SUA can predict two-year incidence of cerebrovascular disease in HD patients. However, SUA levels did not show significant predictive effect on two-year coronary events, peripheral artery disease and cardiovascular mortality.

Artificial-Intelligence-Assisted Discovery of Genetic Factors for Precision Medicine of Antiplatelet Therapy in Diabetic Peripheral Artery Disease

An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients.

Vorapaxar for Prevention of Major Adverse Cardiovascular and Limb Events in Peripheral Artery Disease

Peripheral artery disease (PAD) is a severe manifestation of atherosclerosis. Patients with PAD are at heightened risk for atherothrombotic complications, including myocardial infarction and stroke (MACE); however, there is also an equal or greater risk of major adverse limb events (MALE), such as acute limb ischemia (ALI) and major amputation. Therefore, there is a need for effective medical therapies to reduce the risk of both MACE and MALE. Recent trials have demonstrated the role of thrombin inhibition in reducing the risk of MACE and MALE in PAD patients. One such medical therapy, vorapaxar, is a potent inhibitor of protease activated receptor-1 which mediates the cellular effects of thrombin. Vorapaxar, used in addition to aspirin, has demonstrated robust reductions in MACE and MALE in PAD patients. In this article, we provide a contemporary review of the current state of PAD and the role of antithrombotic medications in the treatment of PAD, as well as the current clinical data on vorapaxar and strategies to integrate vorapaxar into contemporary medical management of peripheral artery disease.