Early determinants of cardiovascular risk in the young: Two Dutch cohorts

Abstract

Cardiovascular disease is the major cause of death in westernized societies, responsible for 35.5% of the total mortality in The Netherlands. Part of the current decline in cardiovascular mortality has been attributed to primary prevention in adults. However, as the roots of cardiovascular disease are in early life, the possibilities for prevention in childhood may be considered. To study early cardiovascular determinants and possible prevention stategies the Atherosclerosis Risk in Young Adults (ARYA) study was designed, consisting of more than 1000 young adults of around 30 years of age selected from the general population. Routine data at birth, childhood and adolescence of 750 subjects was collected from school health records. Of 262 subjects biannual and standardized measurements of cardiovascular risk factors during adolescence were collected by the Municipal Health Service. Recently, cardiovascular risk factors and vascular damage were remeasured. One of the possible early cardiovascular determinants is low birth weight, a concept known as the "fetal origins hypothesis" . Our data show that homozygous carriers of a functional polymorphism in the promoter region of the IGF-I gene show a increased cardiovascular risk factor levels at young age but not with birth weight. Furthermore, we found that the first born children of non-carrier parents weighed on average 584 gram less than homozygous parents, indicating that the IGF-I gene may be related to the fetal growth of their newborns. Our further analyses support the fetal origins hypothesis, as an average decrease in birth weight (540 gram) was associated with one excess coronary heart disease event in 1000 subjects. Also, low birth weight was associated with increased blood pressure, but restricted to those with high attained relative body weights. Next, we observed similar to others that an unfavorable intra-uterine environment may be less important for future hypertension than an excess gain in body weight in later life. Postmortem studies showed that the subclinical process of atherosclerosis was more pronounced in the young with increased risk factor levels. Our findings in healthy young subjects strengthen these findings by showing that systolic blood pressure and pulse pressure at adolescence were positively associated with arterial thickening, a marker for generalized atherosclerosis. The results were independent of blood pressure, gender, age and body mass index. We confirm the finding that adolescent blood pressure in boys and girls predicts hypertension 15 years later. Measuring the blood pressure once, multiple times, routinely or standardized did not affect this prediction. In addition to others, a single routine blood pressure measurement in young adolescent girls could distinguish 60% of the hypertensive women at young adulthood. In young adolescent boys, blood pressure did not distinguish young adults with and without hypertension, but an elevated blood pressure predicted 10-year cardiovascular risk in young adulthood as estimated by the cardiovascular risk profile. We conclude that there is evidence to support the fetal origins hypothesis. A relative low birth weight was associated with an increased blood pressure in young adults with a high body mass, and with an increased risk of a coronary heart disease event. However, a low birth weight was associated with a polymorphism in the promotor region of the IGF-I gene of one of the parents, suggesting that genes may underly the hypothesis. Also, a postnatal change of body size and attained body mass index at young adulthood seems to have a bigger impact on future cardiovascular risk, than birth weight. In addition, in girls a high adolescent blood pressure is able to distinguish those with and without future hypertension. This implies that the Municipal Health Service may consider to re-introduce the blood pressure screening at adolescence, to assess future cardiovascular risk.