Prevalence of hypercholesterolaemia in outpatient children aged 9–11 years

Background:

Hypercholesterolaemia is a silent disease that is considered to be one of the main risk factors for cardiovascular disease, often beginning in childhood, and early diagnosis and management may reduce the risk of developing atherosclerosis and early cardiovascular disease in early adulthood.

Objectives:

The purpose of this study was to evaluate the importance of universal screening for dyslipidemia in children aged 9–11 years.

Methods:

An observational, descriptive, cross-sectional study was conducted from July 2021 to June 2022. A total of 532 children (279 girls and 253 boys) aged 9–11 years were enroled, and non-fasting blood samples were obtained to measure total cholesterol (TC) levels in the blood.

Results:

The mean serum TC was 136.4±28.1 mg/dl. Thirty-two children (6%) of the screened participants had abnormal TC levels; those were tested subsequently by fasting serum TC, and 19 children were confirmed as dyslipidemic (3.5%). The prevalence of borderline blood cholesterol levels (TC between 170 and 199 mg/dl) was 2.6% CI 95% (2.2–3.2), and the prevalence of hypercholesterolaemia (TC ≥200 mg/dl) was 0.9% CI 95% (0.5–1.4). A positive correlation was found between body mass index and blood cholesterol level. (r = 0.55, P =0.002).

Conclusions:

Universal non-fasting TC screening in children aged 9–11 years old is effective in detecting hypercholesterolaemia. Since the authors found that the positive family history as the sole basis for selective examination in children is insufficient.

Introduction

Highlights

• Hypercholesterolaemia is a silent disease that is considered to be one of the main risk factors for cardiovascular disease.

• According to the WHO, the main cause of death globally is cardiovascular disease.

• Universal non-fasting total cholesterol screening in children aged 9–11 years is effective in detecting hypercholesterolaemia.

Dyslipidemia has been linked to early atherosclerosis and cardiovascular disease (CVD)¹. One of the most significant risk factors for the development of CVD, which begins in childhood, is hypercholesterolaemia². In the vast majority of cases, lipid abnormalities are clinically silent, and selective screening alone misses a significant percentage of children with dyslipidemia¹.

The basis for a screening program in children is that early detection and management could help reduce the risk and severity of CVD in young adults¹.

According to the WHO, the main cause of death globally is CVD. According to statistics, 17.9 million individuals worldwide died from CVDs in 2019, contributing to 32% of all mortality³. A report published by the WHO displayed that 4.5% of the global death rate and 2% of disability-adjusted life years in both sexes aged 18 years and over are due to high levels of cholesterol⁴.

About 20% of children in the USA (between the ages of 6 and 19 years) have adverse levels of one or more lipid values. Abnormal lipid levels become more common with age; 15% of children aged 6–11 years and 25% of adolescents aged 12–19 years have at least one abnormal level. The elevated total cholesterol (TC) prevalence is 7.1%⁵.

Cholesterol is a necessary component of cell barrier formation and signalling transduction, both of which are involved in many important physiologic processes. Cholesterol is mainly obtained from two sources: dietary cholesterol (absorbed in the intestine) and intracellularly synthesized cholesterol (mainly synthesized in the liver). Both are delivered to peripheral tissues via a lipoprotein-dependent mechanism once acquired⁶.

Dyslipidemias can be genetically inherited, but they can also be secondary to dietary causes or specific diseases like obesity, type 2 diabetes mellitus, nephrotic syndrome, hypothyroidism, and other causes⁷.

Atherosclerosis, which is assumed to start with arterial endothelial dysfunction and intima-media thickness, is linked to hypercholesterolaemia. Via the injured endothelium lining, lymphocytes and monocytes penetrate and develop into LDL-loaded macrophages and then foam cells, which are balanced by HDL particles. Fatty streaks are an indication of lipid deposition inside the subendothelial lining of the artery wall, which may be reversible⁸.

The first line of management for paediatric dyslipidemia is lifestyle intervention (such as dietary modification and increased physical activity), and the second line is pharmacologic therapy (chiefly with statins). The decision to initiate lipid-lowering therapy is influenced by the type and severity of dyslipidemia as well as the existence of additional CVD risk factors⁹.

Screening subjects only according to a positive family history may miss up to 36% of dyslipidemic children^10,11. The National Heart, Lung, and Blood Institute (NHLBI) of the United States created age-based guidelines for screening children for lipid abnormalities¹.

The lipid profile of Syrian children is largely unexplored. This study aimed to determine the prevalence of hypercholesterolaemia and its associated factors among outpatient children aged 9–11 years at Latakia, Syria.

Methods and patients

An observational descriptive cross-sectional study was conducted from July 2021 to June 2022. The study population included 532 outpatient children aged 9–11 years at Latakia, Syria; 279 girls and 253 boys were enroled, and non-fasting blood samples were obtained. Blood TC was assessed in all participants of the study on the recommendation of an expert panel report released by the NHLBI and endorsed by the American Academy of Pediatrics (AAP)¹. If a lipid abnormality is detected, a fasting sample is used to confirm the diagnosis of paediatric dyslipidemia and determine the need for intervention. All consecutive patients attending the general paediatric clinic at the age of 9–11 years were included. The work has been reported in line with the STROCSS criteria¹².

Ethical approval was obtained from the Scientific Research Directorate according to Decision No. 3959, as well as signed informed consent from the participants’ parents. The questionnaire included the following variables: age, sex, anthropometric measurements (weight and height), past medical history (diabetes, hypothyroidism, metabolic syndrome, liver disease, and kidney disease), and family history (early heart disease in the mother at the age of younger than 65 years or in the father at the age of younger than 55 years, a lipid disorder, diabetes, obesity, and high blood pressure). A clinical examination was performed, BMI was calculated using the calculator provided by the Centers for Disease Control and Prevention (CDC), and a blood sample was obtained for laboratory testing. The specimens were carried out in the central laboratory of the University Hospital. The “Mindray 380” device was used to measure TC.

The levels of lipid were categorized into three groups: the high TC group was defined as having a TC greater than or equal to 200 mg/dl; the borderline TC group was defined as having a TC between 170 and 199 mg/dl; and the acceptable TC group was defined as having a TC less than 170 mg/dl¹.

Results were communicated to the parents. Those with hypercholesterolaemia were referred to the paediatric endocrinology clinic for follow-up.

Statistical analysis

The data were analyzed using the Statistical Package for Social Science (SPSS) software version 20 with a 95% CI and a margin of error of 5%. The qualitative variables are expressed as a percentage, while the quantitative variables are represented by an average±SD. A value of P less than 0.05 is considered significant. The inferential statistics were calculated using the prevalence rate, Paired t-Student to compare the means of two paired groups; independent t-Student to compare the means of two independent groups. A Pearson Correlation test was used to assess the relationship between two continuous variables.

Results

Demographic and clinical characteristics of the study participants

The study included 532 participants, with 279 (52.4%) girls and 253 (47.6%) boys with an average age of 10.11±0.7 years. Table 1 displays the participant distribution based on body mass index; 81.7% of participants are categorized as underweight. Seventeen children had a past medical history [diabetes mellitus (2.1%), hypothyroidism (0.9%), and metabolic syndrome (0.2%)]. and 101 children (18.9%) had a positive family history: obesity 39 (7.3%), hypertension 31 (5.8%), diabetes mellitus 19 (3.6%), dyslipidemia 7 (1.3%), and premature coronary artery disease 5 (0.9%).

Table 1.

Distribution of the study participants according to body mass index

BMI	N (%)
Underweight	435 (81.7)
Normal	92 (17.3)
Overweight	3 (0.6)
Obese	2 (0.4)
Total	532 (100)

N, number of participants.

The mean value of TC was 136.4±28.1 mg/dl. There was a significant statistical difference in TC mean values between two groups of children classified according to the presence of a family history of obesity, arterial hypertension, and dyslipidemia (Table 2). Furthermore, there was no statistical difference in the mean values of TC based on sex or medical history. A positive correlation was found between body mass index and blood cholesterol level. (r = 0.55, P =0.002).

Table 2.

Mean values of blood cholesterol according to the presence of family history in the study

Positive family history	Mean±SD	P
Obesity
Yes	151.66±29.8	0.02
No	135.81±27.9
Dyslipidemia
Yes	144.2±50.7	0.04
No	132.5±27.8
Arterial hypertension
Yes	149.1±28.3	0.04
No	131.1±28.1
Premature coronary artery disease
Yes	135.2±19.3	0.9
No	136.4±28.2
Diabetes mellitus
Yes	137.52±22.3	0.8
No	136.42±28.3

Statistically significant correlation of cardiovascular risk factors using the Pearson correlation, P<0.05.

Following non-fasting cholesterol screening, 32 (6%) of the 532 tested children had abnormal TC levels. Among the 32 children who underwent follow-up testing using a fasting cholesterol level, 19 children (3.5%) were confirmed as dyslipidemic. The prevalence of borderline blood cholesterol levels (TC between 170 and 199 mg/dl) was 2.6% CI 95% (3.2–2.2), and the prevalence of hypercholesterolaemia (TC ≥200 mg/dl) was 0.9% CI 95% (1.4–0.5).

The characteristics of dyslipidemic children based on gender, positive family history, BMI, and medical history are presented in Table 3.

Table 3.

Characteristics of dyslipidemic children

Independents variables	N (%)
Sex
Male	9 (47.36)
Female	10 (52.63)
Positive family history
Obesity	4 (21.05)
Hypertension	2 (10.52
Dyslipidemia	1 (5.26)
No family history	12 (63.15)
BMI
Overweight	3 (15.78)
Normal weight	16 (84.21)
Medical history
Hypothyroidism	1 (5.26)
No medical history	18 (94.73)

N, number of participants.

There was no statistically significant difference (P=0.09) in mean TC levels between fasting and non-fasting 32 participants.

Discussion

Although the atherosclerotic process starts in childhood and fatty streaks first appear in the aorta between the ages of 5 and 20, it does not become observable until later in life; therefore, it has become obvious that preventive measures should begin in childhood¹³.

We found that the overall prevalence of hypercholesterolaemia is 0.9%, which is significantly lower compared with other studies in the USA , Germany, Saudi Arabia, and China^14–17.

Muratova et al. ¹⁴ reported in the USA that the prevalence of hypercholesterolaemia among fifth-grade children was 14.4%. The high prevalence of obesity in American children, the typical American lifestyle with a high-fat diet and sedentary life, and the significant high percentage of overweight children (40%) in Muratova and colleagues study who had a BMI greater than 85th percentile may all be contributing factors to this high prevalence of hypercholesterolaemia.

The prevalence of hypercholesterolaemia in Dathan et al. ¹⁵ study in Germany was 7.8%. While the prevalence in AlMuhaidib et al. ¹⁶ study in Saudi Arabia was 6.7%. and in Wang et al. ¹⁷ study in China, the prevalence of hypercholesterolaemia was 5.4%.

These differences can be attributed to differences in methodology (age range, reference lipid level), lifestyle factors such as dietary habits, demographic characteristics such as variations in distribution based on BMI, and genetic background.

The prevalence of 0.9% of hypercholesterolaemia in our study is believed to be due to a significant difference in the distribution of BMI in favour of the underweight (81.7%) and the age group below adolescence. Lifestyle factors such as dietary habits (the plant-based Mediterranean diet), demographic characteristics, and low income due to the economic crisis in Syria may play a role in it.

We noticed a significant relationship between TC and BMI (r = 0.55, P =0.002). Lipid levels are affected by obesity. This conclusion corresponds with findings from other studies. Manios et al. ¹⁸ reported that among Turkish schoolchildren, overweight boys had significantly higher levels of TC.

The National Health and Nutrition Examination Survey in America (NHANES) found that the likelihood of having abnormal lipid values was higher in adolescents with a greater BMI¹⁹. Similar results have been reported among schoolchildren in Muratova and colleagues, Dathan and colleagues, and Wang and colleagues’ studies^14,15,17. However, due to the low percentage of obesity and overweight in our study, we were unable to establish a link between hypercholesterolaemia and a high BMI.

We found that only seven of the 19 children with dyslipidemia had a positive family history, while the other 12 did not. This suggests that we would have skipped 12 kids (63.15%) with abnormal cholesterol values if we had only relied on a positive family history as the sole basis for selective examination of children. This conclusion corresponds with findings from other studies^10,11.

We did not find any statistically significant differences in mean TC levels between the two groups of fasting and non-fasting participants, which is consistent with the findings of the Langsted A. et al. ²⁰ study, which found there are negligible and clinically irrelevant variations in TC and HDL-C values between fasted and non-fasted states. This conclusion is important because non-fasting lipid levels are often more practical as a screening test for paediatric patients because many patients and families find it challenging to comply with fasting.

Conclusion

The significance of this study lies in the fact that it emphasizes the importance of cholesterol screening according to international recommendations for age groups since we found that the positive family history as the sole basis for selective examination in children is insufficient.

Limitations of the study

Some limitations of this study should be acknowledged, including the need for a complete assessment of the children’s lipid profiles as well as studies involving wider age groups and analyzing the diets of the participants in order to obtain a more accurate estimate.

Ethical approval

Ethical approval was obtained from the Scientific Research Directorate at Tishreen University according to Decision No. 3959, as well as signed informed consent from the participants' parents.

Consent

Written informed consent was obtained from the participants' parents for publication of this study. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Source of funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contribution

N.I. contributed in data interpretation, writing the paper, and in performing an extensive literature review. A.C. and Y.Z. contributed in as mentors and reviewers for this study.

Conflicts of interest disclosure

All of the authors declare that they have no competing interests.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Dr. Nour Ibrahim.

Data availability statement

There was not any datasets generated during and/or analyzed during the current study are publicly available, available upon reasonable request. data sharing is applicable to this article.

Provenance and peer review

Not commissioned, externally peer-reviewed.