Atherosclerosis is a chronic inflammatory vascular disease and the predominant cause of heart attack and ischemic stroke. Despite the well-known sexual dimorphism in the incidence and complications ...of atherosclerosis, there are relatively limited data in the clinical and preclinical literature to rigorously address mechanisms underlying sex as a biological variable in atherosclerosis. In multiple histological and imaging studies, overall plaque burden and markers of inflammation appear to be greater in men than women and are predictive of cardiovascular events. However, while younger women are relatively protected from cardiovascular disease, by the seventh decade, the incidence of myocardial infarction in women ultimately surpasses that of men, suggesting an interaction between sex and age. Most preclinical studies in animal atherosclerosis models do not examine both sexes, and even in those that do, well-powered direct statistical comparisons for sex as an independent variable remain rare. This article reviews the available data. Overall, male animals appear to have more inflamed yet smaller plaques compared to female animals. Plaque inflammation is often used as a surrogate end point for plaque vulnerability in animals. The available data support the notion that rather than plaque size, plaque inflammation may be more relevant in assessing sex-specific mechanisms since the findings correlate with the sex difference in ischemic events and mortality and thus may be more reflective of the human condition. Overall, the number of preclinical studies directly comparing plaque inflammation between the sexes is extremely limited relative to the vast literature exploring atherosclerosis mechanisms. Failure to include both sexes and to address age in mechanistic atherosclerosis studies are missed opportunities to uncover underlying sex-specific mechanisms. Understanding the mechanisms driving sex as a biological variable in atherosclerotic disease is critical to future precision medicine strategies to mitigate what is still the leading cause of death of men and women worldwide.
Vascular Complications of Diabetes Beckman, Joshua A; Creager, Mark A
Circulation research,
2016-May-27, 2016-05-27, 20160527, Volume:
118, Issue:
11
Journal Article
Peer reviewed
Open access
Over the last several decades, the global incidence and prevalence of diabetes mellitus has increased significantly. The raised incidence rate is projected to continue as greater numbers of persons ...adopt a Western lifestyle and diet. Patients with diabetes mellitus are at heightened risk of both adverse microvascular and cardiovascular events. Moreover, once cardiovascular disease develops, diabetes mellitus exacerbates progression and worsens outcomes. The medical management of patients with diabetes mellitus mandates comprehensive risk factor modification and antiplatelet therapy. Recent clinical trials of new medical therapies continue to inform the care of patients with diabetes mellitus to reduce both cardiovascular morbidity and mortality.
Hyperglycemia and insulin resistance are key players in the development of atherosclerosis and its complications. A large body of evidence suggest that metabolic abnormalities cause overproduction of ...reactive oxygen species (ROS). In turn, ROS, via endothelial dysfunction and inflammation, play a major role in precipitating diabetic vascular disease. A better understanding of ROS-generating pathways may provide the basis to develop novel therapeutic strategies against vascular complications in this setting. Part I of this review will focus on the most current advances in the pathophysiological mechanisms of vascular disease: (i) emerging role of endothelium in obesity-induced insulin resistance; (ii) hyperglycemia-dependent microRNAs deregulation and impairment of vascular repair capacities; (iii) alterations of coagulation, platelet reactivity, and microparticle release; (iv) epigenetic-driven transcription of ROS-generating and proinflammatory genes. Taken together these novel insights point to the development of mechanism-based therapeutic strategies as a promising option to prevent cardiovascular complications in diabetes.
Effective revascularization of the patient with peripheral artery disease is about more than the procedure. The approach to the patient with symptom-limiting intermittent claudication or ...limb-threatening ischemia begins with understanding the population at risk and variation in clinical presentation. The urgency of revascularization varies significantly by presentation; from patients with intermittent claudication who should undergo structured exercise rehabilitation before revascularization (if needed) to those with acute limb ischemia, a medical emergency, who require revascularization within hours. Recent years have seen the rapid development of new tools including wires, catheters, drug-eluting technology, specialized balloons, and biomimetic stents. Open surgical bypass remains an important option for those with advanced disease. The strategy and techniques employed vary by clinical presentation, lesion location, and lesion severity. There is limited level 1 evidence to guide practice, but factors that determine technical success and anatomic durability are largely understood and incorporated into decision-making. Following revascularization, medical therapy to reduce adverse limb outcomes and a surveillance plan should be put in place. There are many hurdles to overcome to improve the efficacy of lower extremity revascularization, such as restenosis, calcification, microvascular disease, silent embolization, and tools for perfusion assessment. This review highlights the current state of revascularization in peripheral artery disease with an eye toward technologies at the cusp, which may significantly impact current practice.
Peripheral artery disease affects approximately 10 million people in the United States and more than 230 million people globally.
1
Atherosclerotic occlusive disease involving the leg reduces ...ambulatory function. When symptoms become severe, the clinical manifestation is termed chronic limb-threatening ischemia (CLTI) and is characterized by limb pain at rest, nonhealing skin ulcers, or gangrene. Large randomized, controlled clinical trials have shown that 10 to 20% of patients with CLTI undergo amputation during the 2.5 to 3 years after treatment.
2,3
These results reflect care provided at expert centers, which suggests that outcomes may be even worse for most patients.
4
The tools . . .
In part II of this review, we describe the epidemiology and clinical consequences of vascular disease in patients with diabetes, and discuss the efficacy of risk factor modification and antiplatelet ...treatment. Specifically, evidence-based cardiovascular therapies are discussed through novel clinical insights on management of hyperglycaemia, hypertension, dyslipidaemia as well as platelet dysfunction. Recent trends in the incidence and outcomes of vascular disease in diabetes suggest that timely and effective implementation of therapies is making a favourable impact.
It is estimated that >2 million patients are living with an amputation in the United States. Peripheral artery disease (PAD) and diabetes mellitus account for the majority of nontraumatic ...amputations. The standard measurement to diagnose PAD is the ankle-brachial index, which integrates all occlusive disease in the limb to create a summary value of limb artery occlusive disease. Despite its accuracy, ankle-brachial index fails to well predict limb outcomes. There is an emerging body of literature that implicates microvascular disease (MVD; ie, retinopathy, nephropathy, neuropathy) as a systemic phenomenon where diagnosis of MVD in one capillary bed implicates microvascular dysfunction systemically. MVD independently associates with lower limb outcomes, regardless of diabetic or PAD status. The presence of PAD and concomitant MVD phenotype reveal a synergistic, rather than simply additive, effect. The higher risk of amputation in patients with MVD, PAD, and concomitant MVD and PAD should prompt aggressive foot surveillance and diagnosis of both conditions to maintain ambulation and prevent amputation in older patients.
Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the ...venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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