ABC | Volume 113, Nº4, October 2019

Updated Updated Cardiovascular Prevention Guideline of the Brazilian Society Of Cardiology – 2019 Arq Bras Cardiol. 2019; 113(4):787-891 cholesterol-lowering drugs in lower extremity PAD will be available in the future. x. Glycemic Control: Optimized glycemic control is indicated in all diabetics with lower extremity PAD, especially those with greater severity, such as critical lower limb ischemia. 482,483,484 The objective is to reduce ischemic events in the lower extremities. 483 In addition to their efficacy in glycemic control, new hypoglycemic drugs have been required to demonstrate CV safety. In the EMPA-REG study, the SGLT-2 inhibitor empagliflozin reduced the risk of CV death by 38%. A recent subanalysis of this study showed that in patients with lower extremity PAD at the start of the trial, the risk of lower limb amputation in the empagliflozin group was not significantly different from placebo (HR = 0.84; 95% confidence interval 0.54 and 1.32).506 However, the CANVAS study with canagliflozin, despite a 14% reduction in the risk of the primary combined outcome (CV death, AMI and nonfatal stroke), showed almost doubling of amputations, predominantly at the toe or metatarsal level. (6.3 [canagliflozin] compared with 3.4 / 1000 patient years [placebo]; hazard ratio = 1.97; 95% confidence interval between 1.41 and 2.75). 57 Inversely, the recent DECLARE study TIMI507, with dapagliflozin, in addition to showing reduced CVD death or hospitalizations for heart failure, did not significantly increase the risk of amputations (1.4% in the dapagliflozin group versus 1.3% in placebo; p = 0.53). 507 While further analysis is awaited, it is important that patients using SGLT-2 inhibitors maintain routine preventive foot care and adequate hydration. Monitoring the patient with lower extremity PAD at risk of foot infections, ulcer, gangrene or osteomyelitis is critical. R i s k Fa c t o r s / The r apeu t i c Conduc t and t he i r Recommendation Classes/ Lower extremity PAD Evidence Levels, according to the latest international Peripheral Artery Disease guidelines, are listed in Chart 10.3. 10.6. Autoimmune Diseases and Cardiovascular Risk Several autoimmune diseases can affect the heart through various manifestations including arrhythmias, pericardial, myocardial and coronary artery diseases. In relation to this last complication, advances and research in the field of atherosclerosis have increasingly reinforced the participation of the immune system in its pathophysiology. The presence of lymphocytes and macrophages within atheromatous plaques suggests that inflammation is a major factor in the disease evolution cascade. This hypothesis even motivated a recent clinical trial that evaluated the effect of low dose methotrexate on the reduction of CV events in patients without autoimmune diseases but with previous infarction. Although the reduction in the primary outcome was not achieved in this study, further work in this area is still ongoing. However, in patients with rheumatic diseases, the systemic inflammatory process is amplified and which may result in the occurrence of accelerated atherosclerosis. 509 This condition may be the main explanation for the high percentages of morbidity and mortality in these patients. 510 In addition, the use of certain immunosuppressive medications, such as corticosteroids, may also contribute to the worsening of the CV risk profile. It is worth mentioning RA and systemic lupus erythematosus (SLE) among the diseases that may have this pathophysiological feature, although other conditions such as scleroderma, inflammatory bowel diseases, psoriasis and certain primary vasculitis such as polyangeitis granulomatosis, are also relevant. 509-511 RA is associated with a 3-fold reduction in survival, with ischemic heart disease accounting for about 40% of deaths. 512 In addition, the risk of AMI is about 2 times higher than in the general population, and the prognosis after the event tends to be worse. This scenario begins to develop at the onset of the disease and independently of other factors classically associated with atherosclerosis. Vascular inflammation caused by autoimmunity seems to play a more important role in this context. Some population studies even suggest a recent reduction in CV lethality in these patients, perhaps due to the greater availability of disease-specific treatments. 513 Nevertheless, functional limitation and consequent physical inactivity imposed by RA may also increase the likelihood of developing other risk factors, such as obesity, hypertension and diabetes. On the other hand, it is noteworthy that systemic inflammation in individuals with RA can reduce serum levels of total cholesterol and LDL, promoting what is known as the “lipid paradox”, since the risk of events remains high even with this metabolic profile. 513,514 Nevertheless, control of traditional risk factors remains the main strategy for preventing CV events in these patients. Like RA, SLE also behaves as an independent risk factor for CV disease, with a coronary disease prevalence of up to 10% and a risk of events up to 8 times higher than the general population. Some studies suggest that AMI may be the cause of death in up to 25% of cases, especially in patients who have the disease for longer. 509 At the same time, the prevalence of major CV risk factors such as hypertension, diabetes, obesity, physical inactivity and dyslipidemia is also higher in individuals with SLE. Frequent use of corticosteroids for disease management is another condition that worsens the metabolic profile, although daily doses of prednisone below 10 mg appear to be safe in this respect, as do antimalarial drugs. 515 Nevertheless, risk calculators using traditional factors often underestimate the incidence of events in these patients. Other markers associated with atherosclerosis that are more relevant in individuals with SLE, such as osteoprotegerin and osteopontin, are promising predictors that could refine this estimate. The fact that disease-associated coronary artery disease is more often associated with atherosclerosis than vasculitis corroborates this expectation. 516 As most autoimmune diseases are more common among women, a thorough stratification of CV risk in females is essential in the presence of these conditions, despite the limitations already mentioned. Even so, the fundamental issue is the absence of clinical studies demonstrating a benefit in treating this group of patients more aggressively. To date, there is no evidence that therapeutic targets for blood pressure, blood glucose, LDL cholesterol, or any other risk factor should be modified due to the presence of an autoimmune disease. The relatively low prevalence of these diseases in the population is the main factor limiting good quality studies to answer these questions. Therefore, each case needs to 847