1 Department of Public Health, Kanazawa Medical University, Ishikawa, Japan.
2 Department of Preventive Medicine, Northwestern University Medical School, Chicago, IL.
3 Department of Welfare Promotion and Epidemiology, Toyama Medical and Pharmaceutical University, Toyama, Japan.
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ABSTRACT |
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birth weight; blood pressure; body height; child; cholesterol; growth
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INTRODUCTION |
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Using the record-linkage method, we were able to construct a long term follow-up database of anthropometric indexes from birth to age 20 years and data on blood pressure and serum total cholesterol level at age 20 years in a large population of Japanese. In this study, we investigated whether birth weight, as an indicator of environment during pregnancy, and childhood growth, especially rate of height increase in childhood, are independently related to these major cardiovascular disease risk factors in adult life.
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MATERIALS AND METHODS |
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Between 1949 and 1994, the Ishikawa prefectural government performed medical checkups for all residents aged 20 years. During the period 19851994, 8,741 people (4,182 men and 4,559 women; 44 percent of the 20,001 residents of the area) aged 20 years who were born in 19651974 received this checkup. Blood pressure, serum total cholesterol, height, and weight were measured on this occasion.
At the medical checkup given at age 20 years, blood pressure readings were taken from the right arm by well-trained health care nurses using a mercury sphygmomanometer, with the subject sitting, after 5 minutes' rest. Diastolic blood pressure was recorded as Korotkoff phase V. Blood samples were obtained by cubital vein puncture at random times, and serum total cholesterol concentration was analyzed by standard enzymatic methods using an automatic analyzer (model TBA20R; Toshiba Corporation, Tokyo, Japan).
The two databases from the checkups performed in childhood and at age 20 years were linked by name and date of birth using a computer. Linkage was obtained for 5,127 participants (2,432 men and 2,695 women), who comprised 59 percent of the participants examined at age 20 years. The remaining participants aged 20 years who did not have data from checkups performed at birth were considered to have moved into the area subsequently. Thirty-eight percent of subjects evaluated as babies had subsequent measurements made at age 20. Among those persons, we mainly analyzed data on 4,626 participants (2,198 men and 2,428 women) for whom we had complete data on anthropometric indexes at birth, age 3 years, and age 20 years and cardiovascular disease risk factors at age 20.
We calculated body mass index (weight (kg)/height (m)2) to evaluate overweight at each age. To evaluate growth rate in each period between birth, age 3 months, age 1 year, age 3 years, and age 20 years, we calculated the percentage increase of weight and height in each period. Pearson correlation coefficients were calculated for correlations between cardiovascular disease risk factors at age 20 and anthropometric indexes and their changes in childhood. Multiple linear regression analysis was used to adjust associations of important anthropometric indexes with blood pressure and serum cholesterol at age 20. Multivariate-adjusted differences (and 95 percent confidence intervals) in blood pressure and serum cholesterol associated with a 1-standard-deviation higher value of each factor were evaluated using ß-coefficients from regression analysis. A two-tailed p value less than 0.05 was considered statistically significant. Statistical analyses were performed using the Statistical Analysis System (SAS Institute, Inc., Cary, North Carolina).
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RESULTS |
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Table 1 shows mean values for anthropometric indexes and their changes in childhood and cardiovascular disease risk factors at age 20. At almost all ages from birth to 20 years, men were heavier and taller than women. Percentage increases in weight and height from age 3 years to age 20 years were higher in men than in women.
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There was a significant inverse correlation between birth weight and systolic blood pressure at age 20 years in men (table 2). The other simple correlation coefficients for correlations between birth weight and adult blood pressure were not statistically significant. Adult blood pressure was positively correlated with weight and height from age 3 years and with weight increase after age 3. Adult blood pressure was inversely correlated with percent height increase from age 3 to age 20 in both sexes.
Serum cholesterol concentration showed no significant correlation with birth weight (tables 2 and 3). It was correlated positively with percent weight increase from age 3 to age 20 and with weight and body mass index at age 20. There was an inverse association of cholesterol with percent height increase from age 3 to age 20 in both sexes and with height at age 20 in men.
Multiple linear regression analysis was used to adjust associations of important anthropometric indexes with blood pressure and serum cholesterol. We selected birth weight as an indicator of environment during pregnancy and percent increase in height from age 3 to age 20 as an indicator of environment that is responsible for growth in childhood and adolescence. We included two other confounding factors in the model: gestational age and weight at age 20. We did not include height and body mass index at age 20 in the model, because we considered that both height and obesity at age 20, which are significantly related to percent height increase from age 3 to age 20, are consequences of rate of height increase in childhood. Model 1 included birth weight, weight at age 20, and gestational age. Model 2 included percent increase in height from age 3 to age 20 in addition to the variables in model 1.
In model 1 regression analysis, birth weight was inversely and significantly associated with systolic blood pressure (p < 0.0001 in both sexes) and serum cholesterol (p < 0.0001 in men; p = 0.02 in women), after adjustment for current weight. In model 2 analysis, inverse relations of birth weight to systolic blood pressure (p < 0.0001 in both sexes) and cholesterol (p < 0.0001 in men; p = 0.03 in women) remained significant; moreover, percent increase in height showed significant inverse relations with systolic blood pressure (p = 0.006 in men; p = 0.01 in women) and cholesterol (p < 0.0001 in men; p = 0.0009 in women). In model 2, diastolic blood pressure showed significant inverse relations with birth weight in men (p = 0.001) and rate of height increase in women (p = 0.002). After the addition of height at age 3 to model 2, the inverse relations of height increase rate to systolic blood pressure and cholesterol remained significant.
Tables 4 and 5 show adjusted differences in blood pressure and serum cholesterol at age 20 years associated with a 1-standard-deviation higher value for each factor, estimated using ß-coefficients in the model 1 and model 2 regression analyses in each sex group. The magnitudes of differences for a 1-standard-deviation higher birth weight were similar in models 1 and 2. It was estimated that a 1-standard-deviation higher rate of height increase was associated with a serum cholesterol level that was lower by 3.3 mg/dl in men and by 1.9 mg/dl in women.
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DISCUSSION |
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An ecologic study by Whincup et al. (22) reported that lower height, higher ponderal index, and higher blood pressure were observed among children aged 811 years in towns with higher cardiovascular disease mortality in the United Kingdom. Since the differences could not be accounted for by differences in birth weight, Whincup et al. suggested that factors operating in the childhood environment rather than in the intrauterine environment are likely to be important in the development of these risk factor differences. However, there have been few within-population studies showing an inverse relation between height and blood pressure, while, among children, a positive relation between the two has been commonly accepted (25
). Longitudinal studies investigating the relation between height increase in childhood and adult blood pressure are needed to explain this discrepancy. Cook et al. (29
) examined blood pressure in subjects aged 2026 years who had been followed up from the age of 10 years and found that blood pressure was related positively to height increase after age 10. However, in their study, they used the absolute value of increase in height, which strongly correlates with adult height itself. During childhood and adolescence, standard deviation tends to increase with age. In addition, it would usually be considered that a child growing with mean minus 1 standard deviation in height at each age has steady and normal growth, as well as another child growing with mean plus 1 standard deviation at each age, who actually has a greater absolute increase in height. Therefore, the same value of absolute height increase is likely to have a different meaning between taller and shorter children at baseline. To evaluate steady growth in both children with higher initial height and children with lower initial height, it would be appropriate to use the rate of increase in height that we used in the present study. Using this index, we could demonstrate an independent and inverse association between rate of height increase and adult blood pressure. In fact, the relation was independent of initial height at age 3.
Previous studies showing a relation between birth weight and subsequent blood pressure have been performed in Western countries (16
). Although Hashimoto et al. (30
) demonstrated an inverse relation between birth weight and systolic blood pressure at age 3 years in Japanese children, there have been few studies investigating adult blood pressure in Eastern populations. In this study, we were able to show an inverse association between birth weight and blood pressure among young adults in a Japanese population. It has been observed in many previous studies that the statistical significance of the relation between birth weight and blood pressure gets stronger when the relation is adjusted for current body size, such as body weight or body mass index. This tendency, which was also observed in our study, might be due to a positive correlation between birth size and size at each adult age and a positive correlation between current size and current blood pressure. According to studies carried out in Western populations (1
, 2
), the magnitude of the blood pressure difference by birth weight rose with increasing age. Decreases in systolic blood pressure, adjusted for current size, per kilogram of increase in birth weight were estimated at approximately 23 mmHg in children and 45 mmHg in middle-aged or older adults (1
, 2
). Using our data from tables 4 and 5
, it is estimated that systolic blood pressure was lower by 3.6 mmHg in men and by 2.3 mmHg in women per 1-kg higher increment of birth weight. Although few large-scale studies in young adults have been performed, even in Western populations (1
), the magnitude of the association in Japanese young adults might be similar to that in Western people. Our results, considering gestational age, might also suggest that being small for gestational age affects cardiovascular disease risk factors undesirably.
Although previous studies have demonstrated a relation between low birth weight and coronary heart disease in later life (1115
), whether birth weight relates to serum cholesterol concentration, which is one of the major coronary disease risk factors, is not clear. Some small-scale follow-up studies showed an association of birth weight or abdominal circumference at birth with serum triglyceride, high density lipoprotein cholesterol, or low density lipoprotein cholesterol concentrations (9
, 10
). In the present study, we found that birth weight was associated with adult cholesterol level when adjusted for current weight and rate of height increase in childhood. With regard to cholesterol and height, cross-sectional studies conducted in children aged 9 years (27
) and in subjects aged 1259 years (28
) showed inverse relations. Our study showed that serum cholesterol level at age 20 correlated more strongly with rate of height increase after age 3 than with height at age 20 (tables 2 and 3) and that this relation was independent of other factors (tables 4 and 5). Relatively poor growth in childhood and adolescence might elevate future serum cholesterol concentration.
Although there have been many studies investigating the tracking of obesity from childhood to adult life (31), very few population-based studies so far have reported that a lower rate of height increase during childhood and adolescence relates to adult obesity. However, it is suggested that the imbalance of growth between height and weight during adolescence will cause obesity (32
). This relation might be one of the mechanisms connecting environment during childhood with blood pressure and cholesterol in later life.
In the multiple regression analysis, we faced a problem in selecting confounding factors to include in the model. We did not include height and body mass index at age 20 in the model, because we considered that height and body mass index at age 20, which are significantly related to percent height increase from age 3 to age 20, are consequences of growth in childhood and adolescence. In addition, weight and body mass index at age 20 correlate very strongly with each other (0.90 in men and 0.86 in women), and the coefficients for correlations of weight to blood pressure and cholesterol are almost the same as those for body mass index. Therefore, we used weight at age 20 years to adjust for the effect of current body mass.
In this study, we could not examine some factors that may have confounded the results, such as maternal height, weight, blood pressure, and serum cholesterol level or family histories of hypertension and hyperlipidemia. In addition, we did not have data on the socioeconomic circumstances of the study subjects. In addition to socioeconomic and hereditary factors, lifestyle factors in childhood and adolescencee.g., nutritional intake or physical activitywould have influenced the rate of height increase. The effect of these environmental factors in adolescence on subsequent cardiovascular disease risk factors should be investigated. Moreover, neither birth length, anthropometric indexes between age 3 and age 20, nor cardiovascular disease risk factors during childhood were determined in this study. Recording of gestational age in months, not weeks, was also one of the limitations of this study. Investigations of height increase at more detailed intervals are necessary.
Some studies of subjects followed from birth to adulthood have raised the question of selection bias (33, 34
). Such long term follow-up studies were based on a relatively small fraction of the original cohort. We considered this problem in the case of our study using the record-linkage method. However, we think that our data were reliable, for several reasons. First, our study subjects represented a relatively larger portion of a general population in comparison with other studies. Especially, almost all babies in our study area received checkups. Second, there were no significant differences either in the proportion of low birth weight infants or in gestational age, childhood height, and childhood weight between those who were linked and those who were not. In addition, there were no significant differences in blood pressure, serum total cholesterol, height, weight, or body mass index at age 20 between those who were linked and those who were not. Third, in our study area, almost all residents and migrants were Japanese, and no significantly different characteristics related to socioeconomic status were likely to exist as compared with migrants or subjects who did not receive the medical checkup. Although residents who were interested in their health might have been more likely to have a checkup at age 20, this would probably not have influenced the study results, because the prevalence of any disease is usually very low among people aged 20 years in the general population. Fourth, because infant and child mortality has been very low in Japan (35
), the number of cases withdrawn due to death during the follow-up period would have been very few. Hence, selection bias is not likely to have influenced the results of the present study.
In this study of Japanese young adults, both birth weight and rate of height increase in childhood and adolescence were inversely and independently associated with blood pressure and serum cholesterol level. The study also found that a lower rate of height increase was related to a higher body mass index in adult life. These results suggest that both environment during pregnancy and environment during childhood and adolescence are independently associated with subsequent cardiovascular disease risk factors. The relation between rate of height increase, rather than current height, and cardiovascular mortality or morbidity should be investigated further.
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ACKNOWLEDGMENTS |
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The authors thank Drs. Masami Nishi, Akemi Ikawa, and Hiroko Kawashima (Ishikawa prefectural government) for data collection, and they acknowledge Dr. Kiang Liu (Northwestern University, Chicago, Illinois) for his important contribution.
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NOTES |
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REFERENCES |
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