Peripheral artery disease (PAD) affects more than 200 million adults worldwide. Patients with lower extremity PAD have a heightened risk for cardiovascular events because of the systemic nature of ...atherosclerosis, and benefit from treatment with risk factor-modifying therapies. Limb symptoms in PAD include intermittent claudication and diminished walking ability. Arterial obstruction from atherosclerotic lesions initiates limb ischemia; however, decreased perfusion incompletely determines the clinical expression of PAD and its response to therapy. Potential mechanistic drivers of claudication in addition to arterial obstruction include inflammation, vascular dysfunction, reduced microvascular flow, impaired angiogenesis, and altered skeletal muscle function. An improved understanding of the pathophysiology of limb symptoms has the potential to accelerate development of novel therapeutic strategies to increase functional capacity in patients with PAD.
Vascular Complications of Diabetes Beckman, Joshua A; Creager, Mark A
Circulation research,
2016-May-27, Letnik:
118, Številka:
11
Journal Article
Recenzirano
Odprti dostop
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.
Peripheral artery disease (PAD) stems from atherosclerosis of lower extremity arteries with resultant arterial narrowing or occlusion. The most severe form of PAD is termed chronic limb-threatening ...ischemia and carries a significant risk of limb loss and cardiovascular mortality. Diabetes mellitus is known to increase the incidence of PAD, accelerate disease progression, and increase disease severity. Patients with concomitant diabetes mellitus and PAD are at high risk for major complications, such as amputation. Despite a decrease in the overall number of amputations performed annually in the United States, amputation rates among those with both diabetes mellitus and PAD have remained stable or even increased in high-risk subgroups. Within this cohort, there is significant regional, racial/ethnic, and socioeconomic variation in amputation risk. Specifically, residents of rural areas, African-American and Native American patients, and those of low socioeconomic status carry the highest risk of amputation. The burden of amputation is severe, with 5-year mortality rates exceeding those of many malignancies. Furthermore, caring for patients with PAD and diabetes mellitus imposes a significant cost to the healthcare system-estimated to range from $84 billion to $380 billion annually. Efforts to improve the quality of care for those with PAD and diabetes mellitus must focus on the subgroups at high risk for amputation and the disparities they face in the receipt of both preventive and interventional cardiovascular care. Better understanding of these social, economic, and structural barriers will prove to be crucial for cardiovascular physicians striving to better care for patients facing this challenging combination of chronic diseases.
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.
Cardiovascular disease (CVD) is the leading global cause of death, accounting for 17.3 million deaths per year. Preventive treatment that reduces CVD by even a small percentage can substantially ...reduce, nationally and globally, the number of people who develop CVD and the costs of caring for them. This American Heart Association presidential advisory on dietary fats and CVD reviews and discusses the scientific evidence, including the most recent studies, on the effects of dietary saturated fat intake and its replacement by other types of fats and carbohydrates on CVD. In summary, randomized controlled trials that lowered intake of dietary saturated fat and replaced it with polyunsaturated vegetable oil reduced CVD by ≈30%, similar to the reduction achieved by statin treatment. Prospective observational studies in many populations showed that lower intake of saturated fat coupled with higher intake of polyunsaturated and monounsaturated fat is associated with lower rates of CVD and of other major causes of death and all-cause mortality. In contrast, replacement of saturated fat with mostly refined carbohydrates and sugars is not associated with lower rates of CVD and did not reduce CVD in clinical trials. Replacement of saturated with unsaturated fats lowers low-density lipoprotein cholesterol, a cause of atherosclerosis, linking biological evidence with incidence of CVD in populations and in clinical trials. Taking into consideration the totality of the scientific evidence, satisfying rigorous criteria for causality, we conclude strongly that lowering intake of saturated fat and replacing it with unsaturated fats, especially polyunsaturated fats, will lower the incidence of CVD. This recommended shift from saturated to unsaturated fats should occur simultaneously in an overall healthful dietary pattern such as DASH (Dietary Approaches to Stop Hypertension) or the Mediterranean diet as emphasized by the 2013 American Heart Association/American College of Cardiology lifestyle guidelines and the 2015 to 2020 Dietary Guidelines for Americans.
Patients with peripheral artery disease (PAD) are at heightened risk of both systemic cardiovascular adverse events, as well as limb-related morbidity. The optimal management of patients with PAD ...requires a comprehensive treatment strategy incorporating both lifestyle changes, including smoking cessation and exercise, as well as optimal medical therapy. Pharmacological therapies for patients with PAD are targeted both at modifying broad risk factors for major adverse cardiovascular events, as well as reducing limb-related morbidity. Observational data suggest that indicated pharmacological treatments are greatly underutilized in PAD, underscoring the need for improvements in patient identification and care delivery. Ongoing trials of novel therapies in patients with PAD will further inform pharmacological strategies to reduce both systemic cardiovascular risk and limb-related morbidity.
Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis. Modifiable risk factors including cigarette smoking, dyslipidemia, diabetes, poor diet quality, obesity, and physical ...inactivity, along with underlying genetic factors contribute to lower extremity atherosclerosis. Patients with PAD often have coexistent coronary or cerebrovascular disease, and increased likelihood of major adverse cardiovascular events, including myocardial infarction, stroke and cardiovascular death. Patients with PAD often have reduced walking capacity and are at risk of acute and chronic critical limb ischemia leading to major adverse limb events, such as peripheral revascularization or amputation. The presence of polyvascular disease identifies the highest risk patient group for major adverse cardiovascular events, and patients with prior critical limb ischemia, prior lower extremity revascularization, or amputation have a heightened risk of major adverse limb events. Medical therapies have demonstrated efficacy in reducing the risk of major adverse cardiovascular events and major adverse limb events, and improving function in patients with PAD by modulating key disease determining pathways including inflammation, vascular dysfunction, and metabolic disturbances. Treatment with guideline-recommended therapies, including smoking cessation, lipid lowering drugs, optimal glucose control, and antithrombotic medications lowers the incidence of major adverse cardiovascular events and major adverse limb events. Exercise training and cilostazol improve walking capacity. The heterogeneity of risk profile in patients with PAD supports a personalized approach, with consideration of treatment intensification in those at high risk of adverse events. This review highlights the medical therapies currently available to improve outcomes in patients with PAD.
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