Documentos de Académico
Documentos de Profesional
Documentos de Cultura
2015;32(6):2674-2683
ISSN 0212-1611 • CODEN NUHOEQ
S.V.R. 318
Original / Síndrome metabólico
Apolipoproteins and their association with cardiometabolic risk
biomarkers in adolescents
Mellina Neyla de Lima Albuquerque1, Alcides da Silva Diniz1 and Ilma Kruze Grande de Arruda1
1
Department of Nutrition. Federal University of Pernambuco, Recife, Brazil.
2674
The Epi Info program, version 6.04b (WHO/CDC, The sample consisted of 104 individuals. Both gen-
Atlanta, GE, USA) was used, and the data were typed ders were proportionally distributed (p = 0.845). The
in double data entry, and data consistency was veri- median age was 15 years (Interquartile Range = 2.0).
fied by module validate. The statistical analyses were The minimum age was 12 years, and the maximum
done using the Statistical Package for Social Sciences age was 19 years. Regarding socioeconomic and lifes-
– SPSS for Windows, version 13.1 (SPSS Inc., Chica- tyle characteristics, 50.7% of the fathers (CI95%: 38.8-
go, IL, USA). 62.5), and 54.7% (CI95%: 43.6-65.3) of the mothers of
The distribution normality of the continuous va- the studied adolescents did not complete their secon-
riables was tested using Kolmogorov Smirnov’s test. dary education, and 77.0% (CI95%: 66.7-84.8) of the
The concentrations of apoB, apoA-I, apoB/apoA-I families were part of social classes C or D. Only three
rate, AGP, HDL and glucose, as well as the per- adolescents (2.9%, CI95%: 0.8-8.8) were classified as
centage of fat were normally distributed and were smokers, and 64.4% were considered underactive or
described in the form of averages and standard de- sedentary (CI95%: 54.4-73.4).
viations. The variables that were not normally distri- The percentile distribution of apolipoproteins A-I
buted underwent a logarithmic transformation (Ln), and B, as well as the apoB/ApoA-I ratio did not vary
and their normality was retested. Only LDL fraction as a function of variables gender, age, parental level
concentrations were normally distributed and were of education, social class and physical activity. An
described in the form of geometrical averages and observation regarding the mothers’ education level,
confidence intervals of 95%. The other variables sti- however, was that a higher education level was as-
ll presenting a non-Gaussian distribution were des- sociated with lower serum concentrations of ApoA-I
cribed in the form of their medians and interquartile and higher concentrations of the apoB/apoA-I ratio.
ranges. Overweight was found in 35.6% (CI95%: 26.6-45.6)
The adolescents were classified into four groups of the sample, of which 14.4% (CI95%: 8.6-23.0) were
according to the percentile distribution of apolipopro- classified as obese, according to the BMI for age and
teins A-I and B serum concentrations, and the apoB/ gender. Abdominal obesity was found in 27.9% (CI95%:
apoA-I ratio. The analysis of variance (One-Way 19.7-37.7) of the individuals, according to their waist
ANOVA) was used to compare the averages of the circumference, and in 25.0% (CI95%: 17.3-34.6) of the
calculated quartiles when the homoscedasticity crite- adolescents, according to their waist circumference/
ria and normal distribution were met, and Bonferroni’s height ratio. High systolic and/or diastolic blood pres-
test was used later. sure levels were found in 15.4% (CI95%: 9.3-24.1) of
Kruskal Wallis’ and Mann Whitney’s “U” tests were the sample. There were no cases of fasting glycaemia
used when normality or homoscedasticity criteria were suggesting diabetes mellitus (> 7 mMol/L), but 4.8%
not met. In describing the proportions, the binomial (CI95%: 1.8-11.4) of the individuals were found glucose
distribution approximated the normal distribution by intolerant (> 5,6 e < 7 mMol/L) (Table I).
the confidence interval of 95%. In the statistical infe- The demographic, anthropometric, clinical and bio-
rence tests, proportions were compared by Pearson’s chemical characteristics of the participants, according
Chi-square test. The significance level adopted for re- to the percentile distribution of apoA-I, apoB and
jecting the null hypothesis was 5.0%. apoB/apoA-I ratio concentrations, are given in tables
II, III and IV, respectively.
BMI, WC, WC/Height and TAG values and TC/
Ethical Aspects HDL and apoB/apoA-I ratios expressed a statisti-
cally significant reduction with the progress of the
This study was conducted according to the guide- percentile distribution of apoA-I concentrations.
lines laid down in the Declaration of Helsinki and all However, the averages of HDL and apoB, on their
procedures involving human subjects were approved turn, increased significantly from the first to the last
by the Committee of Ethics in Research with Human quartile of the apoA-I concentrations. Both the BMI,
Beings of Lauro Wanderley University Hospital – WC and WC/Height anthropometric variables, and
CEP/HULW at the Federal University of Paraíba [Co- the SBP, TC, LDL, TAG, as well as the CT/HDL
mitê de Ética em Pesquisa em Seres Humanos do Hos- and LDL/HDL indices increased significantly over
pital Universitário Lauro Wanderley – CEP/HULW da the distribution in the quartiles of apoB and apoB/
Universidade Federal da Paraíba], and was approved apoA-I ratio.
as per Record CEP/HULW No. 723/10. AGP serum levels varied only within the quartiles
The adolescents and their guardians were informed of apoB, increasing pari passu with the progress of the
in advance about the objectives and methods to be percentile distribution. Gender, age, fat percentage and
adopted in the research, when contacted before the day glycaemia in the adolescents did not show any signi-
of the collection by the technical team. Written infor- ficant differences within the evaluated quartiles of the
med consent was obtained from all subjects. isolated apolipoproteins and apoB/apoA-I ratio.
tor for myocardial infarction, when compared to the that a high apoB/apoA-I ratio was superior to the con-
TC/HDL and LDL/HDL ratios, especially when the ventional lipid measures (LDL, HDL, LDL/HDL,
lipid levels were within the range of desirable values. non-HDL/HDL) in predicting the abnormal thickness
A prospective study representative of the North of the carotid intimal layer. This study, therefore, un-
American population found that the apoB/apoA-I ratio derlines adolescence as a critical period in life, as be-
was significantly associated with mortality due to co- ing exposed to risk factors may produce long-lasting
ronary artery disease, irrespective of other traditional adverse effects on the arterial health, which corrobora-
risk factors, and that it is a better predictor for cardio- tes the relevance of studies for this age group, such as
vascular disease mortality, when compared to the TC/ the results observed in our population of adolescents
HDL ratio9. in Recife.
Exposure to an unfavourable lipid profile from an The Bogalusa Heart Study4 also demonstrated that
early age might induce arterial effects in the long run28. the thickness of the carotid intimal layer in adults in-
According to The Cardiovascular Risk in Young Finns creases significantly over the quartiles of apo B levels
Study29, the levels of apo B and apo A-I and the apoB/ and apoB/apoA-I index in childhood and adolescence,
apoA-I ratio in adolescence were predictive for chan- which, along with the non-HDL, LDL levels, and the
ges in the arterial health in adulthood, such as thic- TC/HDL ratio, emerged as significant predictors of
ker intimal carotid layer and endothelial dysfunction. this harm to someone’s adult life.
These relations did not depend on the concentrations Despite methodological and age range differences,
of apolipoproteins in the adult life. It was also found similar associations of the lipid variables and both
Apo B Quartiles
I (n = 26) II (n = 26) III (n = 26) IV (n = 26)
Variables1
Standard Standard Standard Standard p
Mean Mean Mean Mean
deviation deviation deviation deviation
Girls (%) 57·7 - 42·3 - 57·7 - 46·2 - 0·580||
Age (years) 15·0* 2·0† 15·0* 2·0† 15·0* 2·0† 15·0* 1·2† 0·651¶
BMI (kg/m²) 21·8a 4·3 21·0a 5·3 22·3a 5·0 27·2b 6·7 0·000**
WC (cm) 68·1 *c
11·7 †
66·7 *c
12·7 †
66·5 *c
16·0 †
87·0 *d
30·9 †
0·002¶
WC/Height 0·4*c 0·1† 0·4*c 0·1† 0,4*c 0·1† 0·5*d 0·2† 0·000¶
Fat (%) 27·2 13·6 25·6 17·6 28·1 9·6 33·2 7·9 0·177**
SBP (mmHg) 110·0*c 10·0† 110·0*c 10·0† 120·0*c 10·0† 120·0*d 22·5† 0·001¶
DBP (mmHg) 70·0* 20·0† 70·0* 12·5† 70·0* 12·5† 80·0* 20·0† 0·052¶
Glucose (mmol/L) 4·6 0·5 4·7 0·5 4·5 0·5 4·7 0·5 0·377**
TC (mmol/L) 3·8*c 0·7† 4·0*c 0·6† 4·1*c 0·3† 4·9*d 1·3† 0·000¶
HDL (mmol/L) 1·2*c 0·3† 1·2*c 0·1† 1·2*c 0·3† 1·1*d 0·1† 0·001¶
LDL (mmol/L) 2·1‡a 1·8-2·4§ 2·1‡a 1·9-2·3§ 2·3‡a 2·1-2·5§ 3·0‡b 2·7-3·3§ 0·000**
TAG (mmol/L) 1·4a 0·7 1·1a 0·4 1·3a 0·7 2·0b 0·7 0·000**
TC/HDL 3·3 *c
1·3 †
3·1 *c
0·4 †
3·3 *d
1·2 †
4·8 *e
1·4 †
0·000¶
LDL/HDL 1·8*c 0·8† 1·8*c 0·4† 1·9*c 0·6† 2·8*d 1·2† 0·000¶
Apo A-I (g/L) 1·7a 0·7 2·5b 0·5 2·8b 0·5 2·7b 0·5 0·000**
ApoB/A-I 0·9a,b 0·2 0·8a 0·3 0·8a 0·2 1·0b 0·2 0·004**
AGP (g/L) 0·7a 0·2 0·7a,b 0·2 0·8ª,b 0·2 0·8b 0·2 0·038**
1
BMI, Body Mass Index; WC, Waist Circumference; WC/Height, Waist Circumference/Height; SBP, Systolic Blood Pressure; DBP, Diastolic
Blood Pressure; TC, Total Cholesterol; TAG, Triglycerides; ApoB, Apolipoprotein B; ApoA-I, Apolipoprotein A-I; AGP, a1-acid glycoprotein;
*
Median; †Interquartile Range; ‡Geometric Mean; §95% Confidence Interval; ||Pearson ‘s Chi-square test; ¶Kruskal-Wallis’ test; **One-Way
ANOVA; a,b, letters ≠ mean averages ≠ at significance level 5.0% (Bonferroni’s test); c,d,e, letters ≠ mean averages ≠ at significance level 5.0%
(Mann-Whitney’s “U” test).
systolic and diastolic blood pressure levels and the been described in the literature as the influence of the
apoB/apoA-I ratio, found in the adolescents studied in early nutritional status as the determining factor for the
Recife, were described in a study involving the adult nutritional status in adulthood31.
Chinese population6. This study revealed that the ave- It is known that overweight in younger ages may
rage of the apoB/apoA-I ratio increased according to lead to the early development of cardiovascular disea-
the number of metabolic syndrome components and se risk factors. The results of our investigation indi-
that, even after the exclusion of the TAG and HDL cate that, in adolescence, the BMI, WC and the WC/
variables, this correlation remained significant, indi- Height ratio tend to increase according to the distribu-
cating that the association of the apoB/apoA-I ratio tion of the apoB/apoA-I index, underlining again that
and metabolic syndrome did not depend on the lipid overweight is consistently associated with cardiome-
components. In addition, there was a positive and sig- tabolic risk.
nificant correlation between the apoB/apoA-I ratio and A large number of risk factors for cardiovascular
variables WC, TAG, SBP and DBP, and a negative and disease, such as dyslipidemia, diabetes and arterial
significant correlation between the apoB/apoA-I ratio hypertension are acquired during childhood and ado-
and HDL. lescence, and tend to persist throughout life. The ini-
Overweight is increasing all over the world and has tial alterations of these factors, even if they are minor,
become a serious public health problem. The preva- associated with the distribution of body fat, determine
lence of obesity in childhood more than doubled in the an unfavourable cardiovascular profile for these young
past 15 years in many regions of the world30, and has individuals31.
Additionally, it is worth to note that 64.4% of the ning apoB and the reverse cholesterol transport slants
studied adolescents of our sample in Recife were unde- towards the development of cardiovascular disease
ractive or sedentary, thus characterizing an important and/or diabetes.
percentage of young individuals taking an additional In the studied population, there was a tendency to
risk behaviour in terms of cardiovascular prognosis. a significant increase in alpha-1-acid glycoprotein,
The role of inflammation in the pathogenesis of along with the evolution of the apoB quartiles, empha-
atherosclerosis and its complications also deserves to sizing the association between the largest number of
be highlighted30. A chronic inflammatory state, develo- pro-atherogenic particles in the plasma and a growing
ped because of the summation of metabolic disorders inflammatory state favouring arterial lesions. This is
and environmental stimuli, induces an acute phase why the evaluation of inflammatory markers, such as
response favouring abnormalities that include altera- the AGP, might be considered a relevant tool to add
tions in the metabolism of lipids and lipoproteins32. useful information to traditional cardiovascular risk
Onat and Hergenç33 found both in the adult and in the markers, such as the lipid profile.
elderly population in Turkey that the prevalence of a The study of apolipoproteins has methodological ad-
pro-inflammatory and pre-oxidative state relates to a vantages to identify other variables of the lipid profile
high prevalence of obesity and metabolic syndrome. and to estimate the LDL fraction using Friedewald’s
In these circumstances, HDL and apoA-I particles equation4. It is possible to accurately measure apoli-
lose their anti-inflammatory and atheroprotective pro- poproteins directly in the plasma using internationally
perties, and the balance between lipoproteins contai- standardized methods34,35, which do not require pre-