Turkish Heart Study

We are continuing to study the low levels of high density lipoproteins (HDL)in Turks, who have the lowest levels of HDL cholesterol (HDL-C), ~37 mg/dl in men and ~43 mg/dl in women, ever reported in a well characterized population (1). The cause of the low HDL-C levels is genetic, as Turks living in Turkey, Germany, and the United States have similarly low HDL-C levels, which are associated with elevated hepatic lipase activity (2). Frequently, low HDL-C levels are associated with insulin resistance, but in a study of nonobese, normotriglyceridemic Turks with various HDL C levels, no association was observed between insulin level, plasma glucose concentration, and HDL-C level.

There are kindreds in Turkey in which insulin resistance occurs on a familial basis, and HDL-C levels in affected subjects are often substantially lower than the average values described above for the Turkish population. In recently completed studies, we observed that the subfraction of HDL that is reduced in Turks was the larger HDL subfraction (HDL₂ or LpAI) (3). This is of particular interest because reduced levels of LpAI (and of HDL₂) are associated with increased risk of coronary heart disease (CHD). Recently it has been established that low HDL-C levels are a risk factor for CHD in Turkish men.

To learn more about the etiology of low HDL-C levels in Turks and to characterize the age at which low HDL-C levels can be detected, we studied HDL-C levels in
neonates (cord blood) and prepubescent school children and compared these results with similar data for children of western European descent. Anthropometric and plasma lipid data were obtained for 105 newborns delivered by cesarean section at the American Hospital in Istanbul (Table 1). All the children were healthy products of normal pregnancies and uncomplicated deliveries. The values for total cholesterol (~60 mg/dl), low density lipoprotein cholesterol (~24 mg/dl), triglycerides (~24 mg/dl), and HDL-C (~30 mg/dl) were similar to those of children of western European descent. No gender-related differences in HDL-C levels were observed.

Children 8–10 years of age were also studied to determine if HDL-C levels are lower in prepubescent Turkish children than in children of western European descent. Anthropometric and plasma lipid data were obtained from 225 children in two schools in Ankara, Turkey (Table 2). The schools differed with regard to the socioeconomic status of the students’ families, which was assessed by ascertaining average annual income. Dietary information (food records and recalls) and information about exercise were also collected. The average lipid results of the entire group were total cholesterol ~140 mg/dl and HDL-C ~50 mg/dl, with no significant gender-related differences. Mean values for white American children 5–9 years of age are higher (total cholesterol ~165 mg/dl and HDL-C ~55 mg/dl). However, Turkish children in the higher socioeconomic subgroup had total cholesterol and HDL-C levels similar to those of American children, whereas those in the lower socioeconomic subgroup had substantially lower total cholesterol and HDL-C levels (~130 mg/dl and ~45 mg/dl, respectively). The higher body mass index of the more affluent children suggests that these differences may relate to differences in dietary fat intake. Preliminary analyses of the animal fat, vegetable fat, and total fat intakes showed that less affluent children consumed 20–30% fewer calories as total, saturated, and vegetable fat (data not shown). Socioeconomic status is similarly associated with total cholesterol levels in adult Turks (1).

These observations in Turkish neonates and 8–10-year-old children show that HDL-C levels are not modulated by gender and that total cholesterol and HDL-C levels are similar to those of children of western European descent. In addition, no gender-related differences were observed in total cholesterol and HDL-C levels before puberty in either Turkish or western European children. The effect of socioeconomic status on lipid levels in children and adults has been documented in populations around the world. Lower intake of total fat is associated with lower total cholesterol and HDL-C levels. For example, in the Philippines and Ghana, 7- to 9-year-old boys, who consume 9–10.5% of calories as saturated fat, had total cholesterol levels of 130–150 mg/dl. In contrast, boys of that age in the United States and Finland, where saturated fat accounts for 13–18% of total dietary calories, had total cholesterol values of 165–190 mg/dl.

In prepubescent Turkish children, the 10–13 mg/dl difference in HDL-C between the two socioeconomic groups was striking. It is even more interesting that puberty is associated with 15–20-mg/dl decreases in the HDL-C levels of Turkish boys and girls but is associated with only a 10-mg/dl decrease in American boys and virtually no change in American girls as a consequence of puberty. Furthermore, in Turkish adults there does not appear to be an association between socioeconomic status and HDL-C level.

The mechanism for the significant reduction in HDL-C levels after puberty remains to be determined. It has been speculated that androgen production plays a major role in modulating HDL-C levels at puberty, and increased androgen production is one of the prominent changes at this developmental stage. Consistent with a possible role for androgens in the modulation of HDL-C levels, Turks have lower levels of sex hormone–binding globulin, which theoretically should result in increased levels of free bioactive testosterone in both males and females. Hepatic lipase production is regulated by androgens, and high levels of androgens are associated with increased levels and activity of hepatic lipase. Thus, high levels of free testosterone may explain the high levels of hepatic lipase activity and protein mass that are characteristic of Turkish males and females. This postulate remains to be proven.

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