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Evaluation of Lipid Profiles of Children and Youth from Basic Health Units in Campinas, SP, Brazil: A Cross-Sectional Laboratory Study

Abstract

Background:

Among dyslipidemias, hypercholesterolemia is considered the main risk factor for cardiovascular diseases in adults. In childhood and adolescence, elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are positively associated with atherosclerosis markers, however, systematic screening for dyslipidemias in these groups is a controversial topic.

Objective:

To characterize the frequencies, types and severity of dyslipidemias in children and adolescents attended at the Basic Health Units managed by SUS in Campinas/SP.

Methods:

After an agreement with the Municipal Health Department of Campinas, consecutive results of serum lipid profiles (n = 312,650) of individuals of both sexes (n = 62,530) aged between 1 day old and 19 years were obtained, from 2008 to 2015. Age groups and dyslipidemias were classified according to recommendations in the literature. The statistical significance level adopted was the probability value (p) of 0.05 or less.

Results:

The observed frequencies of increased TC, triglycerides (TG), LDL-C and non-HDL-C (NHDL-C) were 33%, 40%, 29% and 13% respectively, and of reduced high-density lipoprotein cholesterol (HDL-C) the frequency was 39%. The frequencies, in general, were greater in females and in the southwest and south regions of the city, whose populations are more vulnerable from the socioeconomic point of view; on the other hand, in children and adolescents, the frequencies of TG and HDL-C prevailed, respectively.

Conclusions:

The high frequency and regionalization of dyslipidemias in children and adolescents indicate the need for specific actions in the handling and treatment of such diseases by the public health system of Campinas.

Keywords:
Cardiovascular Diseases; Dyslipidemias; Hypercholesterolemia; Child; Young Adult; Unified Health System; Adolescent; Laboratory Test

Resumo

Fundamento:

Dentre as dislipidemias, a hipercolesterolemia é considerada o principal fator de risco para doenças cardiovasculares em adultos. Na infância e adolescência, a elevação de colesterol total (CT) e colesterol da lipoproteína de baixa densidade (LDL-C) associam-se positivamente a marcadores de aterosclerose, entretanto, a triagem sistemática para dislipidemias nestes grupos é um tema controverso.

Objetivos:

Caracterizar as frequências, tipos e gravidade de dislipidemias em crianças e adolescentes atendidos nas Unidades Básicas de Saúde (UBS) mantidas pelo SUS em Campinas/SP.

Métodos: A partir do convênio com a Secretaria Municipal de Saúde de Campinas foram obtidos resultados consecutivos de perfis lipídicos séricos (n = 312.650) de indivíduos de ambos os sexos (n = 62.530), com idade entre 1 dia e 19 anos, entre 2008 e 2015. Grupos etários e dislipidemias foram classificados conforme recomendações da literatura. O nível de significância estatístico considerado significativo foi de p < 0,05.

Resultados:

As frequências observadas de CT, triglicérides (TG), LDL-C e não HDL-C (NHDL-C) aumentados foram, respectivamente 33%, 40%, 29% e 13% e de redução do colesterol da lipoproteína de alta densidade (HDL-C) 39%, no total, sendo maiores no sexo feminino e nas regiões sudoeste e sul da cidade, mais vulneráveis do ponto de vista socioeconômico; já em infantes a de TG, e nos adolescentes a de HDL-C prevaleceram.

Conclusões:

A alta frequência e a regionalização das dislipidemias em crianças e adolescentes apontam para a necessidade de ações específicas no manuseio e tratamento destas no âmbito do sistema público de saúde em Campinas.

Palavras-chave:
Doenças Cardiovasculares; Dislipidemias; Hipercolesterolemia; Criança; Adulto Jovem; Sistema Único de Saúde; Adolescente; Testes Laboratoriais

Introduction

Cardiovascular diseases (CVD) represent one of the main causes of morbidity and mortality in Brazil and worldwide. According to the World Health Organization (WHO), in 2015 CVD accounted for 31% of deaths worldwide.11 World Health Organization (WHO). Cardiovascular diseases (CVDs). 2017; Available from: http://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).
http://www.who.int/en/news-room/fact-she...
In Brazil, 29% of deaths were due to CVD according to the Brazilian Society of Cardiology.22 Sociedade Brasileira de Cardiologia . Cardiômetro: Mortes por doenças cardiovasculares no Brasil. 2015; Available from: http://www.cardiometro.com.br/.
http://www.cardiometro.com.br/...

Dyslipidemias play a well-established role in cardiovascular risk in adults, and so do hypertension, diabetes mellitus, early family history of coronary artery disease and smoking. Often these clinical situations are associated with comorbidities such as overweight, obesity, poor eating habits and physical inactivity, (11 World Health Organization (WHO). Cardiovascular diseases (CVDs). 2017; Available from: http://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).
http://www.who.int/en/news-room/fact-she...
,33 Faludi AA, Izar MC, Saraiva JF, Chacra AP, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol. 2017;109(2 Suppl 1):1-76. with serious consequences for the individual and the public health system. (44 Roth GA, Huffman MD, Moran AE, Feigin V, Mensah GA, Naghavi M, et al. Global and regional patterns in cardiovascular mortality from 1990 to 2013. Circulation. 2015;132(17):1667-78.

Children and adolescents account for 34% of the Brazilian population, an absolute contingent of 57,1 million people. (55 Brasil. Leis, Decretos. Lei n. 8.069, de 13 de julho de 1990, e legislação correlata. Dispõe sobre o Estatuto da Criança e do Adolescente. DOU de 16/07/1990 - ECA; Brasilia,2012. There is evidence that high levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in childhood and adolescence are associated with atherosclerotic outcomes in young adults. In this context, Napoli et al. (66 Napoli C, D'Armiento FP, Mancini FP, Postiglione A, Witztum JL, Palumbo G, et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest. 1997;100(11):2680-90. demonstrated fatty streaks in the intrauterine life span, being more noticeable in pregnant women with hypercholesterolemia.

Unlike the Brazilian Dyslipidemia Directive (DBD) Update, universal lipid screening over two years of age as compared to that of children with risk factors33 Faludi AA, Izar MC, Saraiva JF, Chacra AP, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol. 2017;109(2 Suppl 1):1-76. was recommended, based on other studies, by Zachariah and Johnson77 Zachariah JP, Johnson PK. Pediatric Lipid Management An Earlier Approach. Endocrinol Metab Clin North Am. 2014;43(4):981-92. for having a greater diagnostic sensitivity by 30% to 60%. In Brazil, there are few population studies involving dyslipidemias in childhood and adolescence. (88 Faria-Neto J, Bento V, Baena C, Olandoski M, Goncalves L, Abreu G, et al. ERICA: prevalence of dyslipidemia in Brazilian adolescents. Rev Saude Publica. 2016;50(Suppl 1):10s. In addition, the Study of Cardiovascular Risks in Adolescents (ERICA) stands out, with a national approach and covering a population of 80,000 young people between 12 and 17 years old. (88 Faria-Neto J, Bento V, Baena C, Olandoski M, Goncalves L, Abreu G, et al. ERICA: prevalence of dyslipidemia in Brazilian adolescents. Rev Saude Publica. 2016;50(Suppl 1):10s.

A previous study in our laboratory characterized severe dyslipidemias in the juvenile population in a public hospital segment in Campinas. (99 Faria EC, Dalpino FB, Takata R. Lípides e lipoproteínas séricos em crianças e adolescentes ambulatoriais de um hospital universitário público. Rev Paul Pediatr. 2008;26(1):54-8. However, there are still gaps regarding their characterization in regional terms. Thus, this study was designed to characterize the frequencies, types and severity of dyslipidemias in children and adolescents attended at the Basic Health Units (UBS) in Campinas, SP.

Methods

This is a retrospective cross-sectional study based on monthly lipid profile databases, which were periodically sent to the Lipid Laboratory of the School of Medical Sciences of UNICAMP through an academic agreement with the Municipal Health Department of Campinas.

Between 2008 and 2015 312,650 results of serum laboratory tests were obtained from 62,530 individuals of both sexes, aged between one day and 19 years who visited UBS in the city of Campinas, SP, for medical outpatient care. The UBS are distributed over five regions or health districts of the city.

Only individuals with measured serum lipid profile were included in the study, with the following parameters: TC, triglycerides (TG), LDL-C, high-density lipoprotein cholesterol (HDL-C) and non-HDL-C (NHDL-C). These analyses were performed by enzymatic-colorimetric and/or direct homogenous methods for LDL, according to the quality control standards of the Brazilian Society of Clinical Pathology, including the blood collection stage in the UBS. NHDL-C was calculated. (1010 Xavier HT, Izar MC, Faria Neto JR, Assad MH, Rocha VZ, Sposito AC, et al. V Brazilian Guidelines on Dyslipidemias and Prevention of Atherosclerosis. Arq Bras Cardiol. 2013;101(4 Suppl 1):1-20. A single chemical analyzer, Modular® Analytics Evo (Roche Diagnostics, Burgess Hill, West Sussex, UK), and reagents from Roche Diagnostics® (Mannheim, Germany) were used during the study period.

Dyslipidemias were classified biochemically in consonance with the cut-off values for age advocated by the current DBD33 Faludi AA, Izar MC, Saraiva JF, Chacra AP, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol. 2017;109(2 Suppl 1):1-76. as: isolated increases of LDL-C, TG, NHDL or reductions of HDL-C; mixed dyslipidemias, defined as lipid combinations of increased LDL-C and TG and/or increased LDL-C and reduced HDL-C and/or increased TG and reduced HDL-C.

We used the reference values of Kwiterovich PO1111 Kwiterovich PO. Recognition and management of dyslipidemia in children and adolescents. J Clin Endocrinol Metab. 2008;93(11):4200-9. for infants (children from one day to 23 months of age), once there are no DBD recommendations for this age group, except for TG in the 0-9 years of age group. For NHDL-C in all age groups, also absent in DBD recommendations, the desirable and undesirable values (<123 and ≥144) of Kwiterovich PO were used as well.

In order to determine the groups of children (2-11 years of age) and adolescents (12 to 19 years of age) we followed the Brazilian Child and Adolescent Statute definitions (Law n°. 8.069/90 updated with Law no. 12.010 of 2009), with adaptation of the upper limit for adolescents because of DBD, and the recommendations therein, between two and 19 years of age. (33 Faludi AA, Izar MC, Saraiva JF, Chacra AP, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol. 2017;109(2 Suppl 1):1-76. The cut-off values (mg/dL) used as desirable and undesirable are shown in Table 1.

Table 1
Reference values for lipids and lipoproteins in children and adolescents

Lipid profiles were also evaluated for LDL-C ≥ 190 mg/dL, without concomitant hypertriglyceridemia, for laboratory characterization of possible cases of Familial Hypercholesterolemia (FH). (1010 Xavier HT, Izar MC, Faria Neto JR, Assad MH, Rocha VZ, Sposito AC, et al. V Brazilian Guidelines on Dyslipidemias and Prevention of Atherosclerosis. Arq Bras Cardiol. 2013;101(4 Suppl 1):1-20.

The city of Campinas is a Sao Paulo inland city that has approximately 1.1 million residents, (1212 Johansen IC, Carmo RL, Alves LC. Desigualdade social intraurbana: implicações sobre a epidemia de dengue em Campinas, SP, em 2014. Cad Metrop. 2016;18(36):421-40. with 63 UBS distributed over five health districts: East (E), Northwest (NW), North (N), Southwest (SW) and South (S). (1313 São Paulo. Estado. Secretaria de Saúde de Campinas. Estrutura - SUS Campinas. Campinas: Prefeitura Municipal de Campinas; 2017 [Citado 2018 abr 16] Disponível em: http://www.saude.campinas.sp.gov.br/saude/.

Statistical analysis

The variables, either continuous or categorical, were analyzed using descriptive and comparative tests in software SPSS 24.0 (SPSS Inc., USA) and SAS 9.4 (Inc, Cary, NC, USA). Since there was only one lipid profile available for some individuals and for others several were available during the study, only a single and first lipid profile per year were used in the study period (2008-2015).

Tests were performed to verify the normality of data distribution (Kolmogorov-Smirnov). The groups were then compared by the Mann-Whitney and Kruskal-Wallis tests with Bonferroni post-test, with data presented as median and interquartile ranges for the continuous variables, and chi-square (X2) test with the post-test for multiple comparisons in contingency tables based on permutations for categorical variables. Values of p < 0.05 were considered significant.

Results

Figure 1 shows the distribution of the five health districts of Campinas with the respective numbers observed for test results, of individuals evaluated and their percentage frequencies: East: 41,075 and 8,215 (13%); Northwest: 61,900 and 12,380 (20%); North: 52,975 and 10,595 (17%); Southwest: 79,305 and 15,861 (25%) and South: 77,395 and 15,479 (25%). Half of the tests came from the southwest and south regions.

Figure 1
Corresponding area to the health districts in the map of the city of Campinas.

Table 2 summarizes the demographic characteristics of subjects, including the origin of clinical laboratory calls.

Table 2
Demographic characteristics of all subjects and by sex and age

The results of the descriptive and comparative analyses are shown in Tables 3 and 4.

Tabela 3
Lipid profiles: medians and interquartile ranges for all subjects and stratified by sex and age
Table 4
Lipid profiles: medians and interquartile ranges for all subjects and by regions of campinas

Table 3 shows that in all the age groups, TC, TG, LDL-C and NHDL-C were higher for infants. TG was similar in children and adolescents, and the median of HDL-C levels was higher in children than in the others. In relation to sex, the female group had higher values.

In the comparison by age group, the results also showed significant differences for the parameters evaluated in both sexes.

Table 4 clearly shows that there were higher results for TC in the eastern region than in the other regions. LDL-C levels were higher in the eastern region than in the northwest, southwest and south; NHDL-C values were also higher in this region than in the south and lower in the northwest region than in the others.

In the eastern, north, and southwestern regions, triglyceridemia was higher than in the northwestern region, and in the eastern and southwestern regions, it was higher than in the south. HDL-C in the southwestern region was lower than in the other ones and higher in the eastern region than in the south.

Table 5 shows the frequencies of dyslipidemia and their ratios by sex.

Table 5
Frequencies of isolated and mixed dyslipidemias in all subjects and by sex

The most frequent dyslipidemias were isolated increases in TG and reduction of HDL-C. By sex, dyslipidemia frequencies were higher in females.

Figure 2 shows the frequencies of dyslipidemia by age. Infants presented higher frequencies of increased TG and NHDL-C and isolated dyslipidemias, as well as a higher prevalence of the combination of increased LDL-C and TG.

Figure 2
Frequencies of isolated and mixed dyslipidemias by age; ID: Isolated dyslipidemias; MD: Mixed dyslipidemias; *Chi-Square test (X2); I vs C vs. A; p <0.05; Post-test for multiple comparisons in contingency tables based on permutations: TC↑: LDL-C↑ - C > A = I; TG↑: NHDL-C↑ - I> C > A; HDL-C↓ A> C> I; HDL-C↓ and TG↑ and HDL-C↓ and LDL-C↑ - C> A> I; ID, LDL-C↑ and TG↑: MD-A <C = I; p <0.05. TC: total cholesterol; TG: triglycerides; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; NHDL-C: non high-density lipoprotein cholesterol.

As for children, higher levels of TC and LDL-C were observed, as well as the combination of increased TG and reduced HDL-C; there was also a higher frequency of at least one type of mixed dyslipidemia. On the other hand, adolescents showed a higher number of reduced HDL-C results.

Figure 3 shows the frequencies of dyslipidemia by regions of Campinas.

Figure 3
Frequencies of isolated and mixed dyslipidemias by regions of campinas; ID: Isolated dyslipidemias; MD: Mixed dyslipidemias; *Chi-Square test (X2); E vs NW vs N vs SW vs S; p <0.05; Post-test for multiple comparisons in contingency tables based on permutations: TC↑ = E <others; TG↑, NHDL-C↑ = SW> NW> E; LDL-C↑ = SW > E <NW; HDL-C↓ = SW> others, S> E; ID = NW <SW> S; LDL-C↑ and TG↑ = - NW> L; HDL-C↓ and TG↑ = SW> NW> N> E; MD = SW > NW, p < 0.05. TC: total cholesterol; TG: triglycerides; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; NHDL-C: non high-density lipoprotein cholesterol.

Dyslipidemias were more frequent in the southwestern region of Campinas than in the other regions.

Discussion

The development of atherosclerotic plaques is directly associated with an increase in NHDL-C lipoproteins, and evidence suggests that childhood cardiovascular risk factors such as dyslipidemia may contribute to atherosclerotic disease in childhood and adolescence, as well as in adulthood. (1414 Berenson GS, Srinivasan SR, Bao W, Newman WP, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med. 1998;338(23):1650-6.

In this sense, the ongoing International Childhood Cardiovascular Cohort (i3C) Consortium1515 Dwyer T, Sun C, Magnussen CG, Raitakari OT, Schork NJ, Venn A, et al. Cohort Profile: the international childhood cardiovascular cohort (i3C) consortium. Int J Epidemiol. 2013;42(1):86-96. aims to evaluate the association of the presence of risk factors in childhood with the outcomes of CVD morbidity and mortality in adults. Preliminary results showed that pediatric dyslipidemia predicts dyslipidemia1616 Magnussen CG, Raitakari OT, Thomson R, Juonala M, Patel DA, Viikari JS, et al. Utility of currently recommended pediatric dyslipidemia classifications in predicting dyslipidemia in adulthood: evidence from the Childhood Determinants of Adult Health (CDAH) study, Cardiovascular Risk in Young Finns Study, and Bogalusa Heart Study. Circulation. 2008;117(1):32-42.) and greater carotid intima-media thickness1717 Magnussen CG, Venn A, Thomson R, Juonala M, Srinivasan SR, Viikari JSA, et al. The Association of Pediatric Low- and High-Density Lipoprotein Cholesterol Dyslipidemia Classifications and Change in Dyslipidemia Status With Carotid Intima-Media Thickness in Adulthood Evidence From the Cardiovascular Risk in Young Finns Study, the Bogalusa Heart Study, and the CDAH (Childhood Determinants of Adult Health) Study. J Am Coll Cardiol. 2009;53(10):860-9. in adults. In addition, the presence of risk factors developed from the age of nine was predictive of subclinical atherosclerosis in adults. (1818 Juonala M, Magnussen CG, Venn A, Dwyer T, Burns TL, Davis PH, et al. Influence of Age on Associations Between Childhood Risk Factors and Carotid Intima-Media Thickness in Adulthood The Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Bogalusa Heart Study, and the Muscatine Study for the International Childhood Cardiovascular Cohort (i3C) Consortium. Circulation. 2010;122(24):2514-20.

In the present study, 67% of lipid profile results indicated the presence of at least one type of biochemically classified dyslipidemia. This percentage is greater than the one reported in other national studies: one of them, for example, carried out in the northeastern region of Brazil between 2011 and 2012, involving children and adolescents (6-18 years old), found the frequency of 62% for dyslipidemias with increases in TC and/or TG and/or LDL-C and/or reductions in HDL-C. (1919 Quadros TM, Gordia AP, Silva RC, Silva LR. Predictive capacity of anthropometric indicators for dyslipidemia screening in children and adolescents. J Pediatr. 2015;91(5):455-63. Another study in Londrina/PR with adolescents (11-16 years old) showed that 61% of the subjects had dyslipidemia (elevated TC and/or TG and/or LDL-C and/or reduced HDL-C). (2020 Tomeleri CM, Ronque ER, Silva DR, Cardoso Júnior CG, Fernandes RA, Teixeira DC, et al. Prevalence of dyslipidemia in adolescents: comparison between definitions. Rev Port Cardiol. 2015;34(2):103-9. Also, in 2007 a study of schoolchildren (10-14 years old) from Recife/PE described at least one type of dyslipidemia in 63.8% of the sample. (2121 Pereira PB, Arruda IK, Cavalcanti AM, Diniz AA. Lipid profile of schoolchildren from Recife, PE. Arq Bras Cardiol. 2010;95(5):606-13.

Other works performed in North and South American countries showed lower frequencies. In the United States2222 Nguyen D, Kit B, Carroll M. Abnormal Cholesterol Among Children and Adolescents in the United States, 2011-2014. NCHS Data Brief. 2015 Dec;(228):1-8. between 2011 and 2014, in individuals aged 6 to 19 years, the reported frequency of dyslipidemia was 21% (increased TC and/or NHDL-C and/or reduced HDL-C).

In Santiago, Chile2323 Barja Yáñez S, Arnaiz Gómez P, Villarroel Del Pino L, Domínguez de Landa A, Castillo Valenzuela O, Farías Jofré M, et al. Dyslipidemias in school-age chilean children: prevalence and associated factors. Nutr Hosp. 2015;31(5):2079-87. (2009-2011) in 2,900 individuals aged 10 to 14 years, the frequency of dyslipidemia was 32% (elevated TC and/or TG and/or LDL-C and/or reduced HDL-C). The higher prevalence in the present study may have been caused in part by the lower cut-off values ​​used by the national guideline33 Faludi AA, Izar MC, Saraiva JF, Chacra AP, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose - 2017. Arq Bras Cardiol. 2017;109(2 Suppl 1):1-76. when compared to the international guidelines. (1919 Quadros TM, Gordia AP, Silva RC, Silva LR. Predictive capacity of anthropometric indicators for dyslipidemia screening in children and adolescents. J Pediatr. 2015;91(5):455-63.,2020 Tomeleri CM, Ronque ER, Silva DR, Cardoso Júnior CG, Fernandes RA, Teixeira DC, et al. Prevalence of dyslipidemia in adolescents: comparison between definitions. Rev Port Cardiol. 2015;34(2):103-9.

In the analyses performed to evaluate the effect of sex, dyslipidemias were more frequent for all lipid parameters in females, and these results are consistent with national2424 Franca E, Alves JG. Dyslipidemia among adolescents and children from Pernambuco. Arq Bras Cardiol. 2006;87(6):722-7. and international studies. (2525 Kit BK, Kuklina E, Carroll MD, Ostchega Y, Freedman DS, Ogden CL. Prevalence of and trends in dyslipidemia and blood pressure among US children and adolescents, 1999-2012. JAMA Pediatr. 2015;169(3):272-9. In fact, variations in serum lipoprotein levels are inherent to these individuals in the developmental stages and, consequently, to variations in sex hormones. (2626 Sociedade Brasileira de Cardiologia. I Diretriz de Prevenção da Aterosclerose na Infância e na Adolescência. Arq Bras Cardiol. 2005;85(6):3-36.

Some studies indicate that estrogens increase HDL-C in part due to their action in reducing hepatic lipase (HL) activity and increasing ATP-binding cassette transporter A1 receptors (ABCA1). (2727 Styne DM, Grumbach MM. Physiology and disorders of puberty. Williams Textbook of Endocrinology. 13 th ed. Philadelphia, PA: Elsevier; 2016. In addition, they decrease LDL-C2727 Styne DM, Grumbach MM. Physiology and disorders of puberty. Williams Textbook of Endocrinology. 13 th ed. Philadelphia, PA: Elsevier; 2016. levels by positively regulating LDL receptors, thus exerting a beneficial effect on the lipoprotein profile. (2828 Vashishta S, Gahlot S, Goyal R. Effect of Menstrual Cycle Phases on Plasma Lipid and Lipoprotein Levels in Regularly Menstruating Women. J Clin Diagn Res. 2017;11(5):CC05-7

On the other hand, androgens increase HL activity, leading to an inverse effect: (2727 Styne DM, Grumbach MM. Physiology and disorders of puberty. Williams Textbook of Endocrinology. 13 th ed. Philadelphia, PA: Elsevier; 2016. HDL-C is reduced while LDL-C is increased. In contrast, Zhang et al. (2929 Zhang N, Zhang HQ, Zhang X, Zhang BC, Wang FR, Wang CG, et al. The relationship between endogenous testosterone and lipid profile in middle-aged and elderly Chinese men. Eur J Endocrinol. 2014;170(4):487-94. indicated that testosterone may be associated with changes in SR-B1 receptor and HL activity, facilitating the selective uptake of HDL and playing an antiatherogenic role. (2929 Zhang N, Zhang HQ, Zhang X, Zhang BC, Wang FR, Wang CG, et al. The relationship between endogenous testosterone and lipid profile in middle-aged and elderly Chinese men. Eur J Endocrinol. 2014;170(4):487-94.

Comparisons by age groups revealed that infants presented higher levels of TG, NHDL-C and combination of LDL-C and TG as well as a high frequency of individual dyslipidemias; few studies report this data up to two years of age due to the difficulty of blood collection and metabolic instability in this phase of rapid growth before 24 months of life. (3030 Rabelo LM. Atherosclerotic risk factors in adolescence. J Pediatr. 2001;77(Suppl 2):S153-64. In addition, the high frequency of hypertriglyceridemia would occur through lactation and lack of food fasting. The current DBD defines the cut-off value of TG without fasting for the 0-9 years of age range as ≥ 85 mg/dL. Evaluating this interference, we applied that cut-off value, and the results showed a lower frequency, 56% instead of 67% (≥ 75 mg/dL, with fasting).

In this context, it is also worth noting that according to the national guidelines, (1010 Xavier HT, Izar MC, Faria Neto JR, Assad MH, Rocha VZ, Sposito AC, et al. V Brazilian Guidelines on Dyslipidemias and Prevention of Atherosclerosis. Arq Bras Cardiol. 2013;101(4 Suppl 1):1-20. it is recommended to determine the lipid profile in children and adolescents when: i) grandparents, parents, siblings and first cousins ​​present dyslipidemia, mainly severe or with manifestation of premature atherosclerosis; ii) in the presence of clinical signs of dyslipidemia; in the presence of other cardiovascular risk factors; iii) with involvement of other pathologies, and iv) in the use of contraceptives, immunosuppressants and other drugs that may lead to dyslipidemia. (3131 Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW, Garcia FA, et al. Screening for Lipid Disorders in Children and Adolescents: US Preventive Services Task Force Recommendation Statement. JAMA. 2016;316(6):625-33. Therefore, it is expected that other factors, not collected here, would potentially justify these variations.

As for children, elevated TC and LDL-C were 40% and 35%, respectively. This increase in TC is close to that of a 2009 study with 217 individuals (84 obese), aged 2-9 years in Campina Grande/PB, ranging from 37% to 46%.3232 Ramos AT, Carvalho DF, Gonzaga NC, Cardoso AD, Noronha JA, Cardoso MA. Lipid profile in overweight children and adolescents. Journal of Human Growth and Development. 2011;21(3):780-8. Moreover, this result of TC in children is consistent with data from the National Health and Nutrition Examination Survey (NHANES) of individuals aged 4-19 years, where elevations of TC levels were observed in the 9-11 years age group, decreasing later along the pubertal development. (3333 Hickman T, Briefel R, Carroll M, Rifkind B, Cleeman J, Maurer K, et al. Distributions and trends of serum lipid levels among United States children and adolescents ages 4-19 years: Data from the third National Health and Nutrition Examination Survey. Prev Med. 1998;27(6):879-90.

Ramos et al. (2011) (3232 Ramos AT, Carvalho DF, Gonzaga NC, Cardoso AD, Noronha JA, Cardoso MA. Lipid profile in overweight children and adolescents. Journal of Human Growth and Development. 2011;21(3):780-8. reported that the increase in LDL-C ranged from 14% to 14.8% in children (non-obese and obese), a finding that is lower than that of our study (35%). However, the cut-off value we used is lower than that of the referred population. In addition, similar results were observed in a study in Mexico with children from 2 to 10 years of age: 30% of subjects presented LDL-C ≥ 110 mg/dL. (3434 Bibiloni M, Salas R, Novelo H, Villarreal J, Sureda A, Tur J. Serum Lipid Levels and Dyslipidaemia Prevalence among 2-10 Year-Old Northern Mexican Children. Plos One. 2015.2015;10(3): e0119877.

As for adolescents, there was a high frequency of low HDL-C (41%), a value close to the one reported in the ERICA study, which was 47% among 38,069 schoolchildren, (88 Faria-Neto J, Bento V, Baena C, Olandoski M, Goncalves L, Abreu G, et al. ERICA: prevalence of dyslipidemia in Brazilian adolescents. Rev Saude Publica. 2016;50(Suppl 1):10s. results aligned with those of this study, even considering the different methodological approaches of the two studies.

Other national studies have shown important data. A study conducted in the Northeast, with individuals aged 6 to 18 years, showed a low HDL-C frequency of 41%,1919 Quadros TM, Gordia AP, Silva RC, Silva LR. Predictive capacity of anthropometric indicators for dyslipidemia screening in children and adolescents. J Pediatr. 2015;91(5):455-63. and another one carried out in Natal, RN, with students aged between 10 and 19 showed that 50% of the sample had this type of dyslipidemia. (3535 Vieira Cunha Lima SC, Oliveira Lyra C, Galvão Bacurau Pinheiro L, Medeiros de Azevedo PR, Arrais RF, Campos Pedrosa LF. Association between dyslipidemia and anthropometric indicators in adolescents. Nutr Hosp. 2011;26(2):304-10. Another study conducted in the metropolitan region of Guadalajara, Mexico with 132 individuals aged 5 to 15 years showed a lower prevalence (38.7%), but not very different from our findings. (3636 Romero-Velarde E, Campollo-Rivas O, Celis de la Rosa A, Vásquez-Garibay EM, Castro-Hernández JF, Cruz-Osorio RM. Risk factors for dislypidemia in obese children and adolescents. Salud Publica Mex. 2007;49(2):103-8. The high frequency of reduced HDL-C in adolescents may be associated with young people's lifestyle, which involves inappropriate eating habits, overweight and physical inactivity. (3737 Martinez-Gomez D, Rey-Lopez J, Chillon P, Gomez-Martinez S, Vicente-Rodriguez G, Martin-Matillas M, et al. Excessive TV viewing and cardiovascular disease risk factors in adolescents. The AVENA cross-sectional study. BMC Public Health. 2010 May;10:274.

It is worth mentioning that in this study, 349 individuals presented serum phenotype with LDL-C ≥ 190 mg/dL, that is in 0.56% (1:200) the results were suggestive for FH. (1010 Xavier HT, Izar MC, Faria Neto JR, Assad MH, Rocha VZ, Sposito AC, et al. V Brazilian Guidelines on Dyslipidemias and Prevention of Atherosclerosis. Arq Bras Cardiol. 2013;101(4 Suppl 1):1-20.

In relation to the regions of Campinas, the frequency of dyslipidemias was higher in the south and southwest than in the other regions. According to unpublished reports from the City Hall of Campinas, these regions have the highest number of records (25.7% and 27.6%, respectively) (3838 São Paulo. Estado. Prefeitura de Campinas. Perfil das pessoas e famílias no cadastro unico em Campinas. In: Socioassistencial V, editor. Campinas;2015. in the Cadastro Único, a platform of the Federal Government that characterizes low-income families. In fact, according to Johansen et al., (1212 Johansen IC, Carmo RL, Alves LC. Desigualdade social intraurbana: implicações sobre a epidemia de dengue em Campinas, SP, em 2014. Cad Metrop. 2016;18(36):421-40. they make up the so-called “poverty mountain range”, where there is a socioeconomic homogeneity not observed in the other regions. (3939 Cunha JM, Jakob AA, Jiménez MA, Trad IL. Expansão metropolitana, mobilidade espacial e segregação nos anos 90: o caso da RM de Campinas.In: 11 Encontro nacional da associação nacional de pós graduação em planejamento urbano e regional. Salvador/BA. Anais; 2005. p. 1-21. Additionally, they are the ones that have a greater number of SUS users, accounting for 50% of the test results in this study.

Socioeconomic asymmetry can compromise the lifestyle of populations with direct repercussions on morbidity and mortality indicators. According to the WHO, currently three-quarters of deaths from cardiovascular disease are occurring in low and middle-income regions.1

The ERICA study showed significant increases in dyslipidemias in the north and northeast regions of the country (regions reportedly with the highest poverty indices in Brazil); (4040 Instituto Brasileiro de Geografia e Estatística (IBGE). Síntese de indicadores sociais: uma análise das condições de vida da população brasileira. Rio de Janeiro; 2017. also, ERICA suggests that regional differences in dyslipidemias occur through the process of epidemiological transition, that is, regions may be at different stages. (88 Faria-Neto J, Bento V, Baena C, Olandoski M, Goncalves L, Abreu G, et al. ERICA: prevalence of dyslipidemia in Brazilian adolescents. Rev Saude Publica. 2016;50(Suppl 1):10s.

This study evaluated the second most populous city in the state of São Paulo, located in the southeastern region of Brazil, where urban sprawl occurred without adequate planning and culminated in the expansion of occupation areas with the consequence for the population of inappropriate access to urban services. (1212 Johansen IC, Carmo RL, Alves LC. Desigualdade social intraurbana: implicações sobre a epidemia de dengue em Campinas, SP, em 2014. Cad Metrop. 2016;18(36):421-40.

Limitations of the study

One of the limitations concerns the fact that the evaluated database is of secondary origin, with possible inaccuracies in the insertion of demographic data throughout all the processes. We are aware of the continued use of the quality control standards of the Brazilian Society of Clinical Pathology by the Municipal Laboratory of Campinas, which supplies the laboratory data.

In addition, since it was a cross-sectional study, it was not possible to evaluate the incidence of cases of dyslipidemia.

Conclusion

This study shows the high frequency of atherogenic dyslipidemias in adolescents, children and infants attended in Campinas, with a greater distribution in the less favored socioeconomic regions, indicating the need for a regionalized focus during the development of public health programs for the prevention of early and adulthood CVD, including proper handling and treatment of dyslipidemias.

  • Sources of Funding
    This study was funded by FAPESP process nº 2006/60585-9.
  • Study Association
    This article is part of the thesis of master submitted by Érica Ivana Lázaro Gomes, from Universidade Estadual de Campinas.
  • Ethics approval and consent to participate
    This study was approved by the Ethics Committee of the Unicamp under the protocol number CAAE: 86627418.3.0000.5404 Nº do parecer: 2.662.289. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013.

Acknowledgements

To the Secretaria de Saúde de Campinas for the availability of the database for the study, to the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); protocol 481863/2011-7, and to the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); protocol 2006/60585-9 for the research grants. The authors also are grateful to the Espaço da Escrita - Pró-Reitoria de Pesquisa - UNICAMP - for the translation of the manuscript to English. This study was part of the masters’degree of Erica I. L. Gomes.

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Publication Dates

  • Publication in this collection
    21 Oct 2019
  • Date of issue
    Jan 2020

History

  • Received
    29 June 2018
  • Reviewed
    12 Feb 2019
  • Accepted
    10 Mar 2019
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