Active studies of the main risk factors for cardiovascular disease (CVD) were underway in the 1950s. For more than half a century, data have been accumulated and positive results achieved in both primary and secondary prevention of CVD. The mainstay of primary prevention of circulatory system diseases is lifestyle modification, by correcting leading risk factors and by shaping healthy eating behaviors in patients with CVD. According to the European and Russian guidelines, the principles of proper nutrition include energy balance; macronutrient balance; optimal fatty acid content and ratio; lower salt intake; simple carbohydrate restriction; eating more vegetables and fruits; and widespread use of whole grain foods. The most important point among the above measures is to reduce and optimize the intake of fatty acids that are key risk factors for coronary heart disease and stroke, as shown by a number of large epidemiological studies. However, there are currently increasing amounts of data demonstrating the multidirectional effect of both fats and carbohydrates on the development of cardiovascular disease. This review considers the results of large epidemiological studies, such as PURE, Nurses’ HealthStudy, Health Professionals Follow-Up Study and others, which have investigated the effects, including paradoxical ones, of macronutrients on the development of circulatory system diseases and complications.