Atherosclerosis is a chronic inflammatory process in which the accumulation of cholesterol-laden plaque restricts blood flowin the arterial vasculature. The occlusion of arteries by expanding plaque or emboli from plaque rupture or erosion underlies a variety of cardiovascular diseases including myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral vascular disease. Although cardiovascular disease remains a leading cause of morbidity and mortality in high-income countries, an epidemiological shift has occurred in recent decades.^1,2 Improvements in vaccination and treatment of infectious diseases have led to a notable increase in the prevalence of cardiovascular diseases in low- and middle-income nations.

The prominent and increasing burden of atherosclerotic cardiovascular disease has stimulated growing interest in the elucidation of its pathogenesis, risk factors, prevention, and treatments. There has been remarkable progress in the understanding of atherosclerosis pathophysiology,³ and new risk factors, in addition to traditional ones, have been described to be implicated, including disturbed sleep, physical inactivity, the microbiome, the microbiota and gender-related factors.⁴ Also, knowledge about the importance and possibility of its early prevention, preferably during childhood or even earlier in pregnancy, and about optimized treatment by non-pharmacological therapies,⁵ pharmacotherapy,⁶ and/or interventional procedures,⁷ has expanded, tremendously; but even so, atherosclerotic cardiovascular disease remains the number one killer in the world.²

A fundamental part of any preventive or therapeutic strategy proposed for atherosclerotic cardiovascular diseases is the definition of patient's cardiovascular risk. The Update of the Brazilian Guideline on Dyslipidemias and Cardiovascular Prevention, 2017, suggests a step-by-step approach to identify the risk of each patient. The first step is the identification of the very high-risk patient characterized by the presence of established atherosclerotic cardiovascular disease: coronary, cerebrovascular or peripheral vascular disease.⁸

The American guidelineon the management of blood cholesterol⁹ considers very high-risk patients the ones with a history of multiple major atherosclerotic cardiovascular disease events or history of one major atherosclerotic cardiovascular disease event – acute coronary syndrome episode (within the past 12 months), myocardial infarction (other than recent acute coronary syndrome event listed above), ischemic stroke, symptomatic peripheral arterial disease (claudication with ankle-brachial index <0.85, or previous revascularization or amputation) – and multiple high-risk conditions.

Finally, the European guidelines on the management of dyslipidemias¹⁰ considers as very high-risk patients with documented atherosclerotic cardiovascular disease, either clinical or unequivocal on imaging. Documented atherosclerotic cardiovascular disease includes previous acute coronary syndrome (myocardial infarction or unstable angina), stable angina, coronary revascularization (percutaneous coronary intervention, coronary surgery, and other arterial revascularization procedures), stroke and transient ischemic attack, and peripheral arterial disease. However, in these three guidelines, the definition of risk has been based on the different territories (heart, brain or lower extremities) involved.

In this issue of the International Journal of Cardiovascular Sciences, Picoli et al.¹¹ describe the role of the territory involved in the primary disease territory on the occurrence of secondary disease. The authors had the objective to calculate the statistical probability of developing myocardial infarction, ischemic stroke or peripheral arterial disease after the occurrence of a primary event and its subsequent treatment. Their data included 507,690 patients with primary atherosclerotic disease, who were in treatment during the study period and who developed or did not develop a second atherosclerotic cardiovascular disease event. After searching the literature, they found 6,840 papers that were analyzed according to the first inclusion criterion: 180 studies of patients with clinical and imaging diagnosis of acute myocardial infarction, ischemic stroke and/or peripheral arterial disease. Full text analysis led to the exclusion of 131 papers remaining 49 that were used for data extraction and statistical treatment. After calculating the probabilities, the authors found that 2.99% of patients who presented myocardial infarction as the primary atherosclerotic disease developed ischemic stroke and 2.86% developed peripheral artery disease during or after treatment. Patients diagnosed with ischemic stroke as the primary atherosclerotic disease showed a 0.95% risk for developing myocardial infarction and a 5.07% risk for developing leg ischemic event. Patients diagnosed with peripheral artery disease as the primary atherosclerotic disease showed an 8.79% risk for developing ischemic stroke and a 9.17% risk for myocardial infarction as the secondary atherosclerotic disease. They also calculated the probability of a patient who had an initial event to develop a second one. For a patient who had a myocardial infarction as the primary event, the probability of developing an ischemic stroke or leg ischemia was about 50%, similar to a patient who had peripheral artery disease as the primary event and developed myocardial infarction or ischemic stroke as the second episode. The authors called attention to patients who suffered an ischemic stroke as the primary event for whom the probability of developing peripheral arterial disease was high, about 84%, and myocardial infarction only 16%.

A possible limitation of the study was that the available data do not include the details of treatment offered to each patient. It's currently known that different medical specialties may treat patients differently, often not adequately according to guideline recommendations.^12,13 Furthermore, the papers included in this study came from different services and countries, and available evidence indicate important disparities during patients’ follow-up in different centers.¹⁴ These facts may also influence and explain the different courses of primary atherosclerotic event depending on the territory involved. Also, the paper does no relay practical clinical information about the probability of a patient presenting a recurrent event involving the same territory of the first event (e.g., a myocardial infarction after the first episode involving the heart).

Take-home messages given by the authors are: