Cholesterol levels and prevalence of hypercholesterolemia in Mexican children and teenagers

ATHEROSCLEROSIS

Atherosclerosis 103 (1993) 195-203

Cholesterol levels and prevalence of hypercholesterolemia Mexican children and teenagers

in

I. Lerman-Garber* a, J.A. Septilveda-Amorb, R. Tapia-Conyerb, C. Magos-L6pezb, G. Cardoso-Saldafia”, J. Zamora-Gonzhlez”, B. Salvatierra-Izabab, C. Posadas-Romero” ‘Departmemo de Endocrinologia. Instituto National de Cardiologia “Ignacio Ch6vez “, Juan Badiano 1. Tlalpan, 14080 Mexiro City, Mexico bDireccibn General de Epidemiologia, Secretaria de Salud, Mexico City, Mexico

(Received 28 April 1993; revision received 24 June 1993; accepted 28 June 1993)

Abstract

In Mexico, the incidence and prevalence of coronary heart disease has increased over the past three decades and has become the leading cause of death in some areas of the country. Hypercholesterolemia (HC) is a major risk factor for coronary atherosclerosis and most developed countries currently have public health strategies that attempt to reduce the level of cholesterol. In order to learn the mean total cholesterol values and the prevalence of HC, an epidemiologic survey was carried out in a representative population sample that included men and women aged 1 to 98 years, across the nation. In this report, we present the findings in children and teenagers of both sexes (n = 34369). Considering the country as a whole, the mean serum TC was 147 A 35 mg/dl, the prevalence of borderline hypercholesterolemia (TC between 170 and. 199 mg/dl) was 14.7% and the prevalence of high risk hypercholesterolemia (TC 2 200 mg/dl) was 6.7%. This cross sectional study demonstrated the existence of significant geographic differences in serum TC, with mean state values ranging from 133 mg/dl in the south to 164 mg/dl in the north. The prevalences of high risk hypercholesterolemia was as high as 18.2% in Baja California Norte and as low as 2.5% in the state of Morelos. These geographic differences in total cholesterol and prevalence of hypercholesterolemia were already present at one year of age and persisted throughout childhood and adolescence. Key words: Cholesterol; Hypercholesterolemia;

Children; Mexico

1. Introduction

Although the clinical symptoms of coronary heart disease usually do not occur until the fourth or fifth decade of life, the initial stages of athero* Corresponding author, Tel.: (905) 573-2911 ext 272.

begin in youth [l-5]. The concept of atherosclerosis as a pediatric problem was first proposed more than 20 years ago and it was based on two findings; autopsy studies that showed aortic and coronary atherosclerosis early in life, and evidence that there are important coronary risk factors susceptible to modification. These

sclerosis

0021-9150/93/.SO6.00 0 1993 Elsevier Scientific Publishers Ireland Ltd. All rights reserved SSDI 0021-9 150(93)05109-I

196

factors when present at younger ages often persist into adult life [6-81. One of them, and probably the most important, is serum cholesterol. Prospective epidemiological studies in many countries have established the direct and strong relationship between elevated plasma cholesterol levels and increased prevalence of coronary heart disease. This has been shown in individuals within populations as well as by comparing large populations [9-171. Primary and secondary prevention trials [ 18-221 have established the importance of lowering serum cholesterol levels and this has been translated into a reduction in mortality rates from coronary heart disease. Mexico is in a transition period from being an underdeveloped country. It still has high mortality rates in the neonatal period and early childhood years but there is now an increased life expectancy at birth that has changed from 45 years in 1950 to 65 years in 1980. As a direct consequence of this, there is an increased prevalence of chronic degenerative diseases’ including coronary heart disease. Recent studies have shown that although relatively low, coronary mortality has increased in the last three decades. Actually, for some states in the country, it has become the leading cause of death [23-251. Because we have little information in Mexico about the mean levels of cholesterol and the prevalence of hypercholesterolemia [26-271, a large population survey was undertaken. This article describes our findings in children and teenagers of both sexes. 2. Experimental design and methods The National Serum Epidemiologic Survey was carried out by the General Directorate of Epidemiology of the Ministry of Health from March 1987 to May 1988. The development of the sample frame and the sample draw were based on detailed maps with random household selection across Mexico. A representative population sample of 68 266 individuals that included men and women aged 1 to 98 years across the nation was studied. Of these participants, 34 369 corresponded to subjects 1 to 19 years of age. There were 16 113 boys and 18 256 girls. The population sampled was 30% rural and 70% urban. With sub-

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jects in a nonfasting state, a single blood sample was drawn into sterile vacutainer tubes (ST CAT 6510 from Beckton Dickinson) from all the apparently healthy persons living in each household visited. The clotted blood was then centrifuged and the serum was frozen until analysis at the lipid laboratory of the Endocrinology Department of the National Institute of Cardiology ‘Ignacio Chavez’. Total cholesterol (TC) was measured in a bichromatic autoanalyzer Abbott VP11 using an enzymatic method (Boehringer Mannheim). To enhance the validity of the measurements and the usefulness of the results, our laboratory became enrolled in the standardization program of the Center for Disease Control in Atlanta, GA. The intra- and interassay coefficients of variation were 1.5% and 1.8%, respectively. For the current analysis, Mexico was divided into three regions using Stugers rule [28], and as cut points, percentiles 33.3 and 66.7 of the mean total cholesterol values. Region 1 had the lowest mean TC value, region 2 had an intermediate value and region 3 had the highest mean value. Results in children and teenagers were compared with those found in the adult population (n = 33 897) during the same survey [29]. 2.1. Statistical analysis Simple descriptive statistics (means, standard deviations and correlation coefficients) were used in this cross sectional study. A Student’s t-test and analysis of variance, were used to determine the differences in TC values between regions by age group and gender. Percentile values (5th to 95th percentile) were also calculated. The data base was managed with the Fox Plus program. Percentile values and prevalences were obtained by the program SAS version 6.03. 3. Results Mean values of serum total cholesterol for males and females 1 - 19 years of age in each state of the Mexican Republic are shown in Fig. 1. In Fig. 2 the mean serum TC values for males in the different regions are presented: 137 f 29, 145 f 32 and 153 f 38 mg/dl for regions 1,2 and 3 , respectively (P < 0.0001 when comparing one region

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195-203

150

140

TOTAL CHOLESTEROL

160

170

(MG/DL)

Fig. I, Mean serum total cholesterol values for boys and girls I- 19 years old in the different states of Mexico. Using Stugers rule, Region 1 in white bars, Region 2 in hatched bars. Region 3 in black bars. CHIS, Chiapas n = 1010; GRO, Guerrero n = 865; OAX, Oaxaca n = 849; SLP, San Luis Potosi n = 1086; GTO, Guanajuato n = 1543; QRO, Queretaro n = 889; TLAX. Tlaxcala n = 746; VER, Veracruz n = 1100; NAY, Nayarit n = 770; MICH, Michocan n = 1032; MOR, Morelos n = 634; PUE, Puebla n = 1482; COL, Colima n = 828; HGO, Hidalgo n = 1109; TAB, Tabasco n = 1627; CAMP. Campeche n = 763; NL, Nuevo Leon n = 1864; YUC, Yucatan n = 863; AGS, Aguascalientes n = 754; DGO, Durango n = 1051; MEX, Mexico state n = 1475; COAH, Coahuila n = 951; JAL, Jalisco n = 1869: DF, Distrito Federal n = 1228; QROO, Quintana Roo n = 836; ZAC. Zacatecas n = 1175; TAMP, Tamaulipas n = 963; SON, Sonora n = 1097; CHIH, Chihuahua n = 1027; SIN, Sinaloa n = 1183; BCS. Baja California Sur n = 996; BCN. Baja

California Norte n = 704.

versus the other). Also in Fig. 2, the mean serum TC in females were 142 f 3 1, 148 f 32 and 158 f 38 mg/dl, respectively (P c 0.0001 when the three regions were compared). Borderline hypercholesterolemia, defined as TC > 170 and < 200 mg/dl (75-95th percentile for western populations), was found in 9.8% of the males and 12.5% of the females in region 1, 13.5% and 15%, respectively, in region 2 and 15.8% and 18.7%, respectively, in region 3. High risk hypercholesterolemia, defined as TC > 200 mg/dl, was found in 2.6% of the males and 4.1% of the females in region 1, 5.2% and 5.8%, respectively, in region 2 and 9.7% and 11.8%, respectively, in region 3. Taking the country as a whole, the mean serum TC was 147 f 35 mg/dl, the prevalence of borderline hypercholesterolemia was 14.7% and high risk hypercholesterolemia ocurred in 6.7%. Fig. 3 clearly shows that the differences in mean serum TC between the 3 regions becomes apparent since one year of age and remains constant over

the age span surveyed. Looking more closely at the TC mean values, the trend in both sexes of the different regions was to show a slight increment until lo-12 years of age. At that point, a different pattern was observed between boys and girls. Males had an overall decrement until ages 15- 16 and then returned to a similar or higher cholesterol value by age 18. In contrast, females did not show any decrement but instead, had progressively increased TC values. Serum TC percentile distribution in the 34 369 children and adolescents divided by sex and age group are shown in Table 1. As summarized in this table, females had higher TC levels than males at all the percentile values but this was particularly relevant for the 15-19-year-old group. The mean TC values for each of the 31 states and Mexico City observed in the first two decades of life showed a very high correlation with the mean TC values found for the adult population in each state: r = 0.90, P < 0.001 for males and

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103 (1993) 195-203

FEMALES Region

mean (mddl)

n

BHCT*HRHCT** (%I (%I

1 0

5289

142

12.2

4.1

2 m

5975

148

15.1

5.7

3 m

7005

158

19.9

11.6

MALES n

Region

mean

BHCT* Ii?:

bg/dl) (X)

‘ENTRAL MERICA

10

4443

136

9.8

2 m

5292

144

13.0

5.1

3 m

6363

153

17.2

9.7

Fig. 2. Serum total cholesterol levels and prevalence of hypercholesterolemia in boys and girls in the different regions of Mexico. BHCT, borderline hypercholesterolemia; HRHCT, high risk hypercholesterolemia.

r = 0.89,

P < 0.001 for females. There was a

similar correlation for the prevalence of high risk hypercholesterolemia in the first two decades of life versus adults: r = O.g56, P < 0.0001 for males and r = 0.898, P < 0.0001 for females (Fig. 4).

4. Discussion It is important to understand the values of serum TC including the mean and its percentile distribution during childhood, its trend during dif-

FEMALES

MALES

Fl~lon 2 n = 5252 Rr#on 1 n = 4443

i

v)

1

I

120’ 0

2

4

6

6

IO

I2

AGE (YEARS)

14

I6

IPI

?O

0

?.

4

6

PJ

IO

12

I4

I6

I8

20

Am (YEARS)

Fig. 3. Serum total cholesterol levels in boys and girls in the different regions of Mexico related to age in years.

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Table 1 Serum total cholesterol Percentiles

percentile

distribution

in 34 369 Mexican

children

and teenagers,

ages I to I9

Age (years) and gender l-4

IO-14

5-9

15-19

M

F

M

F

M

n

2722

267 I

5218

5158

4915

F 5722

M 3243

F 4720

5th 10th 50th 75th 90th 95th

95 104 139 162 184 200

96 105 142 164 189 205

98 108 143 165 I88 208

IO1 Ill 145 167 190 208

100 109 141 163 I87 205

102 110 143 164 186 202

99 107 138 160 184 202

106 115 I50 174 201 218

n = number

of children

measured

in each age group.

A 3 240 I ,P

120

130

140

TOTAL CHOLESTEROL

150

160

IN CHILDREN

170

180

(YG/DL)

B

l4YPERCHOLESTEROLEYIA IN CHILDREN (Total cholestwol > 200 YC/DL)

Fig. 4. Correlation of mean serum total cholesterol levels (A) and of the prevalence rates of hypercholesterolemia (B), between children and teenagers with those found in the adult Mexican population. The circles represent the 31 states and the Federal District.

ferent age groups and its correlation with geographic location and the TC values in the adult population. This should be useful not only to the pediatrician but to all of us who are concerned with the impact of atherosclerosis and its various clinical manifestations in the adult population. It has become clear that preventive strategies must start in the early years of life. The reasons for this are as follows. The atherosclerotic process begins in childhood but only becomes clinically manifest later in life [30,31]. Fatty streaks initially appear in the aorta between 5 and 20 years of age [5]. In children and young adults that were followed in the Bogalusa Heart Study [4], both serum cholesterol and low density lipoprotein cholesterol were significantly associated with the extent of aortic fatty streaks (r = 0.67). Secondly, the rationale to support early intervention in childhood is the persistence of lifestyle characteristics developed during this age group that continually contribute to increased cardiovascular risk in adulthood. These include smoking, obesity, inadequate eating habits and a sedentary life style. These characteristics are already associated with adverse lipid profiles during childhood [7,32,33]. This cross sectional study of 34 369 children aged 1- 19 years in Mexico indicates the existence of significant geographic differences in serum TC, with mean values ranging from 133 mg/dl in the south to 164 mg/dl in the north, and prevalences of high risk hypercholesterolemia as high as 18.2% in

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Baja California Norte and as low as 2.5% in the state of Morelos. These differences in total cholesterol and prevalence of hypercholesterolemia were already present at one year of age and remained throughout childhood and adolescence. Although several factors may be playing a role, these lindings are likely to be caused by environmental factors, mainly diet. Diet is a very important factor that modulates the lipid profile in the general population. As has been clearly shown in studies with adult individuals, a higher intake of saturated fats and cholesterol is increased associated with prevalences of hypercholesterolemia and coronary heart disease [9,12,17]. In children, in a more in depth study in 8-9-year-old boys from live different countries [34,35], there was also a signilicant positive correlation between the mean TC per country and the mean proportion of energy intake derived from total fat (r = 0.84). There was also a significant negative correlation with the proportion derived from carbohydrates (r = -0.87). In a multiple regression analysis, the concentration of TC was positively correlated with the percentage of saturated fats in the diet. We believe that the trend for cholesterol values

Table 2 Differences

in mean serum cholesterol

Percentiles

75th percentile

95th percentile

LRC, Lipid Research

we found in this survey is likely to be related to the geographic differences in food intake. The people who live in the northern states of Mexico have a higher income and accessibility to animal derived food products in contrast to the southern states where there is increased poverty and malnutrition [36,37] and the diet is based on corn, beans and chili. In Mexico, the population is mainly mestiza (Indians mixed with Spaniards) with differences in the Indian roots all across the country. Even with this data, we believe that it is likely that genetics do not have a main participation as is demonstrated in studies of the trend of cholesterol values of Japanese populations that migrate to Hawaii or California. Another variable that has been correlated with increased mean TC values in childhood is obesity [38]. In Mexico, we do not have data on the geographic distribution of obesity in childhood, but in adults its prevalence is higher in the northern states of the country. In comparing the percentile distribution of serum TC in Mexico with the values found in other studies like Bogalusa [39], Muscatine [40,41] and the Lipid Research Clinics [42], it can be seen (Table 2) that Mexico has lower mean TC at the

levels (mg/dl) related to age and sex between children

and teenagers

of different

populations

Age (years) and gender 2

50th percentile

103 (1993) 195203

LRC BHS Muscatine Mexico LRC BHS Muscatine Mexico LRC BHS Muscatine Mexico Clinics

7

12

M

F

M

F

155 139

160 143 141 177 161 163 206 193 207

164 159 158 144 180 180 174 166 209 220 204 207

168 168 159 146 184 187 175 167 211 216 203 209

139 176 158 163 209 192 199

(421; BHS, Bogalusa

Heart

Study

[39] and Muscatine

M 160 155 162 143 178 175 179 I64 208 209 218 214 [38].

17 F

M

F

162 165 164 141 179 185 179 162 207 218 213 200

150 153 152 139 170 163 173 160 203 185 212 196

159 149 159 151 177 162 173 174 209 181 217 216

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50th and 75th percentile values for males and females in most of the different age groups. However, the 95th percentile values were very similar. If we compare the country divided by regions (Fig. 2), region 3 disclosed very similar TC percentile values to those found in the American population. There have been several cross sectional studies and a few incomplete longitudinal studies of the changes in lipids and lipoproteins during puberty [7,43-481. When data are pooled together, the general trend is for serum TC levels to increase slightly during childhood until the ages of 9-10 years. At the onset and during puberty, TC decreases both in boys and girls, with more marked and lasting decrements in HDL-C in boys of around 15-22% [42,43]. This interaction appears to be related to changes in sex steroid levels (HDLC is related negatively to testosterone levels in normal pubertal males) [44]. In the present study we found the same pattern for mean TC values in males and even though we could not get data related to pubertal stages we can infer that it is reflected in the TC values. In females, there is instead a minor decrement or plateau in TC after ages 12-13. Longitudinal studies of cohorts of children followed in Beaver County [49], Muscatine [38,41], Bogalusa [49-521, and Tecumesh [53], have examined the correlation and persistence of TC values for periods of up to 16 years. These studies concluded that childhood TC values may have more of a short term variation than adults but long term tracking is similar. Also the correlation decreases with increased length of follow up. Approximately 50-70% of the children in the highest TC percentiles continued to demonstrate the percentiles 8-16 years later [38,50,54,55]. In the present study, given its cross sectional characteristic, we cannot determine if the cholesterol values will maintain the rank order over time (tracking), but we can predict that a significant group of individuals, particularly from the northern states of Mexico, will be hypercholesterolemit when adults. We compared the present data with those found in the Mexican adult population [29]. There was a very good correlation between the mean state serum TC levels found in childhood with those

found in adulthood. In addition, the distribution of mortality rates for ischemic heart disease in the adult population for the different states of Mexico was highly correlated with the mean state TC values and prevalence of hypercholesterolemia in both the young and the adult individuals. Similar data have been obtained from studies in 11 developed countries [56,57]. The slope of the regression equation derived from these studies suggests that lowering the mean TC in 7-8 year old boys in Muscatine (168 mg/dl) to the mean TC in Greece and Portugal (146 and 149 mg/dl, respectively) may be associated with a 38% decrement in ischemic heart disease deaths in middle aged males in the United States. In conclusion, our present findings emphasize the importance of intervention at early ages to modify coronary risk factors. It is especially relevant to focus on the higher risk regions of Mexico, such as the northern states, where preventive measures should have an even greater impact. 5. References I

2

3

4

5 6

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