ABC | Volume 112, Nº5, May 2019

Updated Updated Geriatric Cardiology Guidelines of the Brazilian Society of Cardiology – 2019 Arq Bras Cardiol. 2019; 112(5):649-705 1.10.1. Treating Depression and Anxiety in Patients with Cardiovascular Disease First generation antidepressants include MAOI and tricyclic and tetracyclic antidepressants (TCA and TeCA, respectively); second-generation antidepressants include selective serotonin reuptake inhibitors (SSRI), selective norepinephrine reuptake inhibitors (SNRI), and atypical antidepressants. 89,96 Even though MAOI (phenelzine, tranylcypromine, moclobemide, selegiline, etc.) are effective, they present several unfavorable collateral effects, mainly OH, tachycardia, and hypertensive crises; the latter are also associated with stroke and acute aortic dissection and should, thus, be avoided in patients with CAD. 89,96 The cardiovascular collateral effects of TCA (imipramine, amitriptyline, nortriptyline, desipramine, clomipramine, doxepin, maprotiline, etc.) are fairly well known, namely, increased HR, OH, slowed cardiac conduction, and increased QT interval variability. 89,97 These effects, which have been reported not only in patients with CVD but also in people without previous cardiac disease, in addition to their anticholinergic action, make this class of drugs inappropriate for treating depression in elderly patients. 96 SSRI (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, etc.) are considered the medications of choice for treating depression and anxiety in most cases, due to their acceptable safety profile and higher margins of non-toxic levels in comparison with other classes of antidepressants. 89,96 Regarding efficacy of SSRI in decreasing symptoms of depression, all meta-analyses of selected indicators have shown that these antidepressants are more effective than placebo. 98 SSRI may cause prolonged QT intervals (reported mainly with fluoxetine and citalopram), but they do not generally lead to life-threatening arrhythmias in therapeutic doses. Citalopram appears to be the most cardiotoxic SSRI (conduction disturbances and arrhythmias). 96 Most causes of prolonged QT interval and subsequent torsade de pointes (TdP) induced by SSRI are observed in patients with underlying vulnerabilities, such as congenital long QT syndrome, recent AMI, hypokalemia, or hypomagnesemia, or in cases of substance overdoses. 96 Within this class, there is some evidence that escitalopram and sertraline have the best balance between effectiveness and acceptability for pharmacological treatment of depression in cardiac patients. 99 In summary, SSRI probably do not cause adverse effects when used according to the recommended dosages, and it has been suggested that, through complex mechanisms, they may bring some benefits to the cardiovascular system, such as lower rates of AMI in comparison with other types of antidepressants, especially TCA. 96 As there are still no robust clinical orientations, patient treatments should be individualized in relation to potential risks and benefits. Additional studies are necessary to verify the exact cardiovascular safety profile. 96 Regarding selective serotonin and norepinephrine reuptake inhibitors (SSNRI) (venlafaxine, desvenlafaxine, reboxetine, duloxetine, etc.), venlafaxine is associated with severe cardiotoxicity, only when given in high doses. Left ventricular (LV) failure, even in patients with no prior history of CVD, has also been reported in the literature. 89,96 It is recommended to monitor blood pressure (BP) in patients who take SSNRI (especially venlafaxine), given that it has been reported to increase in epidemiological studies. 96 Regarding atypical antidepressants (mirtazapine, agomelatine, nefazodone, trazodone, etc.), mirtazapine, in high doses, may cause hypotension and affect HR. Trazodone has minimal cholinergic activity; it may cause OH, and, in excess, prolonged QT and slowed atrioventricular conduction. 96 In addition to pharmacological treatment, psychotherapy and the prescription of non-medical treatments, such as physical activity, especially aerobic exercise and cardiac rehabilitation, are also indicated. These improve prognosis and patient quality of life and reduce risks of evolution of CAD and CVD. 89,99 1.11. Other Cardiovascular Risk Factors Traditional risk factors explain only half of CVD cases, which present high morbimortality rates. Several studies have been developed to look for possible new risk factors, known as emerging risk factors, as well as means of early diagnosis of CVD by investigating signs of subclinical atherosclerosis. The emerging risk factors covered in these Guidelines are hyperuricemia, C-reactive protein (CRP), vitamin D, genetic factors, coronary calcium score (CCS), and investigation of subclinical atherosclerosis. 1.11.1. Hyperuricemia Recent epidemiological studies have demonstrated that hyperuricemia is frequently observed in patients with CVD or high risks thereof, such as arterial hypertension, CAD, peripheral vascular disease, HF, and stroke. 100 A recent meta-analysis of observational prospective studies on hyperuricemia and risk of stroke demonstrated a significant increase in the risk of stroke incidence and mortality, based on studies that adjusted traditional stroke risk factors, such as age, sex, hypertension, hypercholesterolemia, and blood glucose. Several pathophysiological mechanisms have been postulated, including endothelial dysfunction, oxidative metabolism, and platelet adhesiveness and aggregation. The role of hyperuricemia as an independent risk factor for CAD, however, remains controversial. 101 1.11.2. C-Reactive Protein The role of inflammation in the propagation of atherosclerosis and susceptibility to adverse cardiovascular events is well established. Even though CRP is involved in the immunological process which triggers vascular remodeling and platelet deposition and is associated with increased CVD risk, there is no definitive evidence for its role as a causal factor of atherothrombosis. The Jupiter study analyzed 9,261 elderly patients of both sexes, using ultrasensitive CRP (US-CRP) levels to determine whether or not they would receive rosuvastatin; the results were similar to those found in younger individuals, namely, a reduced occurrence of cardiovascular events. 102 661