Indian Pediatrics 2003; 40:556-560 

Study of Lipid Profile in Children of Patients with Premature Coronary Artery Disease

Key words: Coronary artery disease, Lipid profile, Pediatric population.

Many studies have demonstrated that atherosclerosis has its silent beginning during childhood(1,2). Fatty streaks are the earliest grossly visible arterial lesions of the atherosclerotic process. Autopsy studies have shown that fatty streaks are the precursors of mature atherosclerotic lesions(3). Coronary artery disease, particularly when it presents early in adult life, has been observed to have a familial tendency. This clustering of coronary artery disease may be partly explained by the familial aggregation of known risk factors because of similar genetic and environmental factors(4). Unknown or newer factors such as fibrinogen, plasminogen activator inhibitor may also contribute(5-7). Of the various risk factors, hyperlipidemia is considered to be one of the major risk factor in the causation of atherosclerosis.

We assessed the incidence and type of lipid disorders in 250 offspring of parents (<55 years of age) with premature coronary artery disease and explored the correlation with lipid levels of the affected parent and with 250 age matched controls.

Subjects and Methods

The study group A included 250 children, of 200 parents being treated at our center for premature coronary artery disease (exertional angina or myocardial infarction), in the age group 5 to 14 years (mean 11.7 ± 1.8 years). The control group B consisted of 250 age-matched children, aged 4-14 years (mean 11.07 ± 1.8 years) who had no parental history of premature coronary artery disease. Information about complete risk factor profile of parents was obtained. All parents and their children underwent complete lipid profile using enzymatic colorimetry method, after 12 hours fasting, and after ruling out the following causes of secondary hypercholes-terolemia i.e., nephrotic syndrome, hypo-thyroidism, parental use of drugs like oral contraceptives, retinoic acid and anticonvul-sants. Serum low density lipoprotein level was estimated using Friedewald’s formula:

LDL cholesterol = Total cholesterol – HDL cholesterol – Triglycerides ÷ 5.

In parents having myocardial infarction, lipid profile was assessed either within 24 hours of acute myocardial infarction (AMI), or after three months of AMI when acute phase reactants were expected to settle down. Cut off points for lipid levels for the children were defined, according to the NCEP guidelines for children, total cholesterol ³ 200 mg%, LDL ³130 mg%, triglycerides ³140 mg% and high density lipoprotein cholesterol level £35 mg%(8). For parents, the cut off values for abnormal lipid levels were considered according to the NCEP guidelines for secondary prevention: total cholesterol >200 mg%, LDL >100 mg%, triglycerides >200 mg% and high density cholesterol <35 mg%(9).

Difference between groups were com-pared with an unpaired Students’ t test. Simple linear regression analysis was applied to examine the relationship between two variables. P <0.05 was considered significant.

Results

The study group consisted of 250 children from 200 parents (males = 195, females = 5) with coronary artery disease. It was seen that in parents (Group A) the prevalence of smoking was the highest, 57.5%(115) followed by other risk factors, obesity 46%(92), diabetes 32%(64), and hypertension 26.5%(53). The age and sex distribution of the parents is shown in Table I. The analysis of lipid profile of children revealed that mean levels of total cholesterol, low density lipoprotein cholesterol and triglycerides were higher in children of affected individuals as compared to controls (P <0.001) where as levels of HDL were lower in cases than controls (P <0.001)(Table II). In total, 74% of study group children had lipid disorder when compared with controls. The most frequent disorder was low high-density lipoprotein cholesterol, seen in 25% followed by increased triglyceride levels, seen in 22.5% (Table III).

Table I

Age and Sex Distribution of Parents with Pemature Coronary Artery Disease

Age (years)	Males	Females
<35 years	5	Nil
35-44 years	106	1
45-54 years	84	4

 

Table II

Lipid Profile of Study and Control Group

	Group A (n = 250)	Group B (n = 250)	P value
Total cholesterol (mg%)	163.6 ± 21.5	143.2 ± 13.5	<0.001
LDL (mg%)	101.4 ± 20.2	80.5 ± 14.7	<0.001
HDL (mg%)	38.8 ± 2.5	41.4 ± 2.4	<0.001
VLDL (mg%)	23.8 ± 5.6	19.8 ± 2.9	<0.001
TG (mg%)	117.8 ± 23.3	99.8 ± 14.37	<0.001

Group A: Children of affected parents; Group B: Age matched controls.

Table III

Type and Incidence of Dyslipidemia in the Affected Parents and their offsprings

Biochemical marker	Parents (n = 200)	Children (n = 250)
­Total cholesterol	51%	10%
­ TG	32.5%	22.5%
­ HDL-C	14%	25%
¯ LDL	70%	10%
­ TG + ¯ HDL	5%	2%
­ TC + ¯ HDL	4.5%	1%
­ TC + ­ LDL	50.5%	4%

 

A comparison of lipid profile of children and their parents was done in two groups. viz., 200 parents and their first child (r), and 50 parents and their second child (r*). This revealed a significant positive correlation with regard to total cholesterol (r = 0.599, P = 0.0001; r* = 0.527, P = 0.0001), HDL (r = 0.185, P = 0.009; r* = 0.407, P = 0.003), low density lipoprotein levels (r = 0.592, P = 0.0001, r* = 0.543, P = 0.0001), and triglyceride levels (r = 0.288, P = 0.0001; r* = 0.360, P = 0.01).

Discussion

Coronary artery disease is mutlifactional and caused by interaction of genetic and environmental factors. Genetic component is believed to be the more predominant factor when coronary atherosclerosis ]presents early in life. In addition, premature coronary artery disease tends to run in families. Although the familial clustering of coronary artery disease is not entirely explained by the familial aggregation of traditional risk factors, hyper-lipidemia contributes to a large extent(4).

Many epidemiological studies have docu-mented the relationship between cholesterol levels and occurrence of coronary artery disease in adults(10,11). Relationship between coronary artery disease and serum cholesterol levels is difficult to evaluate in children because clinically significant coronary artery disease does not occur. On the other hand, early appearance of coronary artery disease in patients with homozygous familial hypercholesterolemia proves that young arteries are not resistant to atherogenic effects of high cholesterol. Coronary artery disease detectable by angiography may occur as early as 18 and 25 years of age in male and female heterozygotes respectively, and as early as 6 years of age in patients of homozygous familial hypercholestero-lemia(12,13).

Strong and McGill(14) studied aortic and coronary lesions in a total of 4737 young subjects (age 10-39 years) included in International Atherosclerosis Project, an autopsy study from 14 different countries. By 10 years of age, the autopsied aorta from all groups had fatty streaks in majority of subjects, and some had coronary fatty streaks.

Our study reveals that premature coronary artery disease patients have significant incidence of hyperlipidemia, and a positive correlation exists between lipid levels of parents and their children. This observation is consistent with the previous studies(15-18). In a study by Blumenthal, et al.(15), of the 72 children whose fathers had myocardial infarction, 13.8% had cholesterol levels greater than 230 mg% whereas there was no signifi-cant difference between mean triglyceride levels.

Rallidis, et al.(17) showed that there was a correlation between lipid levels of parents and their children and the strongest father-offspring correlation was with total cholesterol values. This observation is similar to that reported by Parmar, et al.(18). Lee, et al.(19) studied 173 progeny from 63 families in which father had angiographically diagnosed coronary artery disease by 50 years of age. Age group of studied progeny ranged from 6 to 31 years. 65% of the affected fathers and 51% of progeny had elevated triglyceride, elevated low density lipoprotein cholesterol, decreased high density lipoprotein or combinations thereof. The distribution of lipid abnormalities bore a close resemblance to those observed in the affected fathers. In contrast, Khalil et al.(20), in a study from India compared offspring of patients with proven coronary artery disease (n = 50) and healthy parents (n = 50). There was no difference in the lipid profile of children of both the groups. In another study(21) the mean plasma cholesterol levels and HDL in Indian children were lower than their Western counterparts. The values observed in this study(21) are similar to those in our study group, and that there is a need to establish nomograms of lipid levels for Indian children. Several studies have shown that childhood rank orders of cholesterol are maintained over time, a phenomenon known as tracking(22). Thus, children whose choles-terol levels are high tend in general to have high levels during adulthood, and early diagnosis of dyslipidemia in children provides an opportunity for long-term primary amelioration of risk factors, if introduced at an early age.

We conclude that children of coronary artery disease patients have significant incidence of dyslipidemia compared to age matched controls. There is a positive correlation between lipid levels of patients and their children. Therefore, all children of premature CAD patients should be screened for dyslipidemia, so that dietary measures can be instituted as a first step towards healthy life style.

Contributors: AS provided the framework and concept. She will act as the guarantor. SG collected the data and drafted the manuscript which was edited by AS.

Funding: None.

Competing interests: None stated.

 References