INTRODUCTION

Atherosclerotic cardiovascular disease (CVD) is the leading cause of death and disability in Brazil and worldwide, causing a significant medical, social and economic impact. Atherosclerotic disease has been strongly associated with the presence of certain conditions: cardiovascular risk factors. The accumulation of knowledge in this area has provided insight and, mainly, the basis for more concrete proposals for preventive actions for cardiovascular diseases at increasingly younger ages.

AGGREGATION OF CARDIOVASCULAR RISK FACTORS IN YOUNG PEOPLE

Several studies have been dedicated to the evaluation and prevention of cardiovascular risk factors in childhood and adolescence. Of note is the study by Bogalusa(1,2), Louisiana, United States, which began in 1973 and has made contributions to the present day. This study explores the precursors of CVD that begin in childhood and evaluates genetic and environmental factors that may contribute to the establishment of the disease in adulthood. For this purpose, it studies young people from birth to young adulthood, and is certainly a reference for most of the information and recommendations available for this age group. Other studies, such as the Muscatine, Minneapolis, Canadian studies on Indians, and Finnish studies, among others, also contribute significantly, offering information on populations with distinct ethnic and sociocultural characteristics(3). In Brazil, the Rio de Janeiro study is the longest-lasting study on young populations. It is a line of research on blood pressure (BP) and other cardiovascular risk factors in young individuals and their families that has been developed at the State University of Rio de Janeiro (UERJ) since 1983(4-9).

At young ages, the most investigated risk factors to date are high LDL-C, low HDL-C, arterial hypertension (AH), obesity, diabetes mellitus (DM)/glucose intolerance, smoking, physical inactivity, and family history of some of these factors and/or cardiovascular events at younger ages(3).

Cardiovascular risk factors tend to aggregate and are frequently seen together in the same individual. Epidemiological studies have demonstrated that this association increases the probability of cardiovascular events, since each risk factor tends to reinforce the other and, consequently, the associated morbidity and mortality(10).

This situation is a common reality in clinical practice in adults, but it can also be observed in childhood and persist until young adulthood. The relationship between overweight/obesity and changes in BP and lipid and carbohydrate profiles has been highlighted by several studies, both in adults and in younger populations.

In children and adolescents, obesity has been shown to have important predictive value for BP, total cholesterol and serum lipoproteins(2,11). The study by Bogalusa(1) demonstrated an inverse relationship between HDL-C and obesity. Furthermore, it was observed that children with high HDL-C values ​​had lower BP and LDL-C. In obese adolescents, the presence of intra-abdominal fat was directly related to basal insulinemia and triglycerides, and inversely related to HDL-C, while femoral adipose tissue was inversely correlated with triglycerides and LDL-C(3). In American schoolchildren, the increase in the prevalence of obesity rates between 1975 and 1990 was associated with high prevalence of hypercholesterolemia and higher mean BP(12).

In Brazil, the Rio de Janeiro study demonstrated, in several stages, a strong association between BP and higher anthropometric indices, highlighting that this relationship, in a longitudinal evaluation of adolescents over ten years, was able to indicate a greater aggregation of other cardiovascular risk factors in young adulthood. Other Brazilian authors(13) evaluated children and adolescents and found high rates of lipid alterations and excess weight in children of young parents with coronary artery disease. In Rio Grande do Sul(14), the evaluation of 1,502 children and adolescents between 6 and 16 years old from public and private schools demonstrated an association between the presence of overweight and high cholesterol.

In young adults, the Coronary Artery Risk Development in Young Adults (CARDIA) study demonstrated a positive association between insulin levels and BP, total cholesterol and LDL-C, and a negative association with HDL-C(3,11). In Brazil, Rabelo et al.(15) demonstrated the presence of cardiovascular risk factors in aggregation in young populations between 17 and 25 years old, highlighting the association between high levels of LDL-C, triglycerides with body mass index (BMI) and sedentary lifestyle.

The association between hypertension, dyslipidemia, DM/glucose intolerance and obesity is called metabolic syndrome (MS), and insulin resistance appears to play a central role in its pathophysiology. The combination of these conditions has had several names, such as syndrome X, deadly quartet, insulin resistance syndrome and plurimetabolic syndrome.

In this context, hyperinsulinemia is related to activation of the sympathetic nervous system, increased renal sodium retention, and stimulation of cell growth, all of which are involved in the determination of cardiovascular diseases and risk factors. More recently, the Framingham Offspring Study added important information, describing the association between hyperinsulinemia and factors related to hemostasis (fibrinolysis, thrombosis, and homocysteine) and altered urinary albumin excretion. Since the last two alterations would ultimately represent endothelial injury, these observations would place endothelial dysfunction as part of the expression of insulin resistance(16).

Classically, in more detail, the alterations that make up this syndrome are: overweight/obesity, hypertension, hyperinsulinemia, hyperglycemia, elevated serum triglycerides, and reduced HDL-C. Individuals with this syndrome have high rates of cardiovascular morbidity and mortality.

In younger populations, initial alterations in each of these factors may occur in variable association. However, even if these changes and, mainly, their aggregation are discreet, they give this young person an unfavorable cardiovascular profile(3,4,8,9,11).

In the study by Bogalusa, the evaluation carried out in 4,522 individuals between 5 and 38 years old, selected between 1988 and 1996, for the components of MS (adiposity index, insulin and glucose, triglycerides, HDL-C and BP) found two independent models for the determinism of the syndrome. One of them included insulin/lipids/glucose/adiposity index; the other, only insulin/BP. The two models explained 54.6% of the total variance in the sample, suggesting a relationship between the metabolic alteration and the hemodynamic factor, whose common substrate is hyperinsulinemia/insulin resistance(17).

In the study conducted in Rio de Janeiro, the evaluation of 281 young people, with an estimated mean age of 21 years, for the presence of MS and insulin resistance, using the homeostasis model assessment (HOMA) index, detected 9.3% of the cases as having this syndrome and 18.5% as insulin resistance. It is important to highlight that individuals with these alterations already well identified in such a young age group had, ten years earlier, higher mean BP and BMI than those without MS. In this study, the presence of high BP and overweight or obesity in the 12-year age group determined relative risks of the individual developing MS in ten years of 3.23 and 3.07, respectively.

It is worth highlighting that the presence of multiple risk factors represents a negative factor for the control and progression of each of these conditions(2-4,11).

ATHEROSCLEROSIS IN YOUNG PEOPLE

Evidence that atherosclerosis begins early in life and that its progression to more advanced stages can be observed in young adulthood has been accumulating over the past 50 years.

In 1953, an autopsy study of Korean War soldiers, with a mean age of 22 years, demonstrated the presence of significant coronary atherosclerosis in 77% of cases(18). These findings were later confirmed in a study of soldiers who died in the Vietnam War: an essentially young population that presented atherosclerotic lesions in 45% of cases(19).

In children and adolescents, the first studies were conducted in Americans and Finns and revealed the presence of fatty streaks and thickening of the aortic intima, more rarely before the age of 3 and in practically all children over this age(20). It was later shown that these lesions could even progress to fibrous plaques. In New Orleans, a large study involving 4,737 individuals aged 10 to 39 years demonstrated fatty streaks in the aorta and coronary arteries, detected in a significant percentage of individuals aged 10 to 14 years and in all those over 30 years(2,21). This study found a progressive nature of the lesion’s appearance with increasing age. In 1990, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study published data regarding the evaluation of the aorta and right coronary artery in 390 male individuals aged 15 to 34 years, also demonstrating the presence of fatty streaks and fibrous plaques. In this study, atherosclerotic lesions were found in the abdominal aorta in more than 20% of cases between 15 and 24 years, and from 25 years onwards this percentage increased to more than 30% of cases. In the right coronary artery, the percentages found were lower, in the range of 3% to 4% for individuals aged 15 to 24 years and around 8% for those over 25 years(22). The study by Bogalusa performed autopsies on younger individuals, between 7 and 24 years old, mostly dead from external causes, and lesions such as fatty streaks and fibrous plaques were found in both the coronary artery and the aorta(2,21).

RISK FACTORS AND THEIR RELATIONSHIP WITH ATHEROSCLEROSIS IN YOUNG PEOPLE

When cardiovascular risk factors are evaluated at young ages, the first aspect to be investigated is whether there is a correlation with the atherosclerotic lesions already found in this age group and, even more importantly, with the clinically relevant atherosclerotic disease observed in adults. Thus, it is possible to verify the real importance of its assessment in order to predict greater cardiovascular risk in the future, thus conferring potential value to the detection and intervention on these risk factors since childhood.

The same risk factors that are related to CVD in adults have also been shown to be associated with atherosclerotic lesions in children and young adults, as was well demonstrated in the PDAY(22) and Bogalusa(2,21) studies. The latter correlated its anatomopathological findings with variables obtained prior to death, while the PDAY correlated this with values ​​measured post mortem .

The Bogalusa study also demonstrated that risk factors present ante mortem , such as elevated BMI, systolic blood pressure (SBP), LDL-C and triglycerides, and the presence of smoking, correlated positively with atherosclerotic lesions defined by anatomopathology. Furthermore, the extent of atherosclerotic lesions observed in coronary arteries was greater in young individuals with multiple risk factors. Considering the variables BMI, BP, total cholesterol, HDL-C, LDL-C, triglycerides and smoking, individuals with none, one, two and three or four risk factors presented 19.1%, 30.3%, 37.9% and 35% of the aortic surface with fatty streaks, respectively. The values ​​for these alterations in the coronary artery were, in due order, 1.3%, 2.5%, 7.9% and 11%(2,21).

The PDAY study(22) showed that the atherosclerotic lesions found correlated positively with the levels of total cholesterol and LDL-C, and inversely with those of HDL-C post mortem . Smoking, assessed by means of serum thiocyanate dosages, showed a strong association with more severe atherosclerotic lesions. McGill et al.(23) also related the presence of adiposity and glucose intolerance with atherosclerosis in young people. More recently, the study by Muscatine demonstrated the relationship between BP and the presence of calcifications in the coronary arteries in young adults(24). Using the same methodology, Gidding et al.(25) evaluated 29 adolescents and young adults (11 to 23 years old) with heterozygous familial hypercholesterolemia: seven had calcium deposits in the coronary artery detected by electron emission computed tomography.

All these findings unequivocally demonstrate the association between cardiovascular risk factors and atherosclerotic disease in the first two decades of life, indicating that the greater the number of aggregated risk factors, the greater the severity of coronary and aortic atherosclerotic disease observed in young people.

PRIMARY PREVENTION IN YOUNG PEOPLE

The adoption of primary prevention measures in young individuals is now recognized as being of great importance in the scenario of cardiovascular diseases. Recently, the American Heart Association (AHA)(26) published its recommendations for primary prevention measures for atherosclerotic CVD in childhood. This document emphasizes health promotion, aimed at all children and adolescents, and proposes the identification and adoption of specific measures for children and adolescents at high cardiovascular risk.

The main purpose of preventive cardiology in young populations is to prevent cardiovascular risk factors, more specifically hypertension, dyslipidemia, obesity, diabetes and smoking(3), with broad health promotion measures.

In general, the measures recommended for this age group focus on adopting healthy eating habits that prevent excess calories, salt, saturated fat and cholesterol, regular physical activity and abstaining from smoking (Table 1)(26).

Preventing obesity through diet and regular physical activity is one of the most important tasks, since its success will affect several risk factors, such as dyslipidemia, hypertension and changes in carbohydrate metabolism(2,11).

In addition to correcting excess weight, there are specific dietary recommendations for controlling dyslipidemia that apply to children over 2 years of age. In general, they recommend that 30% of the total calories consumed should come from fat, with a maximum of one third of these calories coming from saturated fat, and no more than 300 mg of cholesterol(3).

To prevent smoking among young people, several programs have been proposed involving families, schools and the entire community, including adult smokers, who should also be targeted by these programs. The same can be said for implementing actions that increase regular physical activity among young people(3,11).

There is currently a consensus that these measures are only likely to be successful if implemented in conjunction with the family, school and community, in a joint effort by the entire society and its government, naturally adapting to the diversity of each population(2,26).

On the other hand, some conditions, when present in a child or adolescent, determine a greater risk for the development of cardiovascular diseases and risk factors. Therefore, the presence of a family history of CVD, especially at an early age, or of at least one identifiable risk factor in this age group and/or habits that are unfavorable for cardiovascular health, such as a sedentary lifestyle and an inadequate diet (excess calories and/or saturated fats and cholesterol), determines a cardiovascular risk profile. This young person should certainly be the target of rigorous monitoring and intervention measures, aiming at modifying the risk factors, which truly constitutes primary prevention, and not just health promotion measures (Tables 2 and 3)(26).

However, some doubts have arisen, questioning the safety and impact of adopting such measures at such early ages, which could compromise the child’s normal growth and development or, adversely, modify the psychosocial environment of the young person and their family(3). With the aim of evaluating the efficacy and safety of a long-term dietary intervention aimed at reducing LDL-C in children with total cholesterol between 80% and 90%, the Dietary Intervention Study in Children (DISC)(27) was initiated in 1987. Six hundred and sixty-three children aged around 9 years were selected. Randomization was applied to usual care (notification of high cholesterol levels and general dietary guidelines) or to the intervention group (group sessions with parents and children for three years, recommending a diet with 28% saturated fat). The efficacy measure was LDL-C levels, while height, ferritin, folate, albumin, triglycerides, HDL-C, sexual maturation, and psychosocial function were safety measures. As a primary outcome, the intervention group achieved a significantly greater reduction in LDL-C, while the results regarding safety measures did not differ between the groups. When dietary care was predominantly carried out by the mother, there was a direct correlation with reduced saturated fat intake by the child(27).

In 1991, the National Heart, Lung, and Blood Institute (NHLBI) initiated the Child and Adolescent Trial for Cardiovascular Health (CATCH)(28), an intervention study for elementary school children aimed at improving dietary quality, increasing physical activity, and promoting abstention from smoking. Total cholesterol levels were the primary assessment measure, although anthropometric indices, BP and heart rate measurements, and HDL-C were also obtained. Each school was randomized to one of three groups: control group, school intervention group, and school and family intervention group. Of the 5,106 children included at baseline, 4,019 were reassessed two and a half years later. The two intervention groups were analyzed together, as there was no difference between them. Overweight was the strongest predictor of adiposity after two and a half years of observation. Those who had a BMI in the 85th percentile at the second assessment also had higher mean total cholesterol, lower HDL-C, and lower performancein the nine-minute run test. Regarding dietary changes, the intervention group showed significant dietary improvements. Total and saturated fat intake decreased, but total cholesterol decreased by only 1 mg/dl in the control and intervention groups. The authors speculated that the reasons for this insignificant lipid change were due to the limited intensity of the intervention (40-minute meetings for 12 to 15 weeks), the short follow-up period (two and a half years), and the non-ideal change in parental behavior.

There is still no confirmation that interventions that promote the reduction of cardiovascular risk in childhood result in effective prevention, or at least in the postponement of a coronary event in adulthood, although all the rationale and evidence to date indicate this direction for health promotion and primary prevention actions.

Therefore, the importance of adopting preventive measures in young populations is based on observations that have clearly established that atherosclerosis is present before the second decade of life, that cardiovascular risk factors are related to these atherosclerotic lesions, and that it is already possible to identify and modify these risk factors in this age group. Only action at this stage of life will be able to effectively guarantee a healthier lifestyle for the cardiovascular system in adulthood.