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Serum cholesterol and cholesterol binding reserve in children of patients of myocardial infarction.
The lipid has been considered as a major threat of developing coronary artery disease, since long. The aortic intima accumulates cholesterol from infiltrating lipoprotein LDL through a damaged endothelium during atherogenesis.[10], [18], [23] HDL was considered as a clearing factor of cholesterol from the wall of aortic intima so it was clear that the decrease in concentration of serum HDL accelerates atherosclerosis.[12] Hsia et al[7] reported that serum has a capacity to solubilize considerable amount of exogenous cholesterol in addition to its own cholesterol content. This capacity of serum was considered as serum cholesterol binding reserve (SCBR). They further reported that SCBR was lower in patients with premature myocardial infarction than in controls. SCBR rose progressively with increasing serum cholesterol or triglyceride among controls but not among the patients. Its value is more significant when hyperlipaemic MI survivors was compared with hyperlipaemic control. In hyperlipidaemic controls it seems that a process of atherogenesis is accelerated by increased serum lipid levels but retarded by expanded SCBR. But in MI survivors due to low concentration of SCBR the process of atherogenesis was accelerated, that is the balance of opposing force was disturbed. Hennekens et al[5], [6] reported that mean cholesterol among children of patients of MI was higher than that of controls but some other workers[1], [8] reported that this difference was not significant. The present study includes estimation of serum cholesterol, SCBR levels of male and female children (1 to 20 years of age) of patients of MI and age and sex matched control children without any history of MI or any other disease which may influence serum lipids to estimate the genetic influence of MI.
The present study was carried out on 818 children (428 male and 390, female) of patients of acute myocardial infarction. The diagnosis of MI was made according to WHO criteria.[25], [26] The age of children varied from 1 to 20, years. None of the case children and the spouse of the patient of MI had any disease or received any medicine which may influence serum lipids. The case children were distributed as follows [Table - 1]. One hundred normal healthy children of normal healthy subjects (age and sex matched) were also included in present study to serve as control. Controls were without any family history of CAD or any other disease which may influence serum lipids. In all these cases, fasting blood samples were drawn for the estimation of total serum cholesterol[27] and its binding reserve.[7]
Control Children In control children the total cholesterol, SCBR and its ratio was found to be 203.82 ±30.52 mg/dl, 85.92 ± 7.71 mg/ dl and 2.37 ± 0.53 respectively. No significant age and sex difference was noticed. Case Children In case children the total cholesterol, SCBR and its ratio was found to be 210.35 ±36.85 mg/dl, 76.2 ± 9.48 mg/ dl and 2.76 ± 0.28 respectively. Serum cholesterol, SCBR levels and their ratio in total case children were compared with that of control children. The level of serum cholesterol in case children were slightly higher but the difference was not significant whereas SCBR level of case children was found to be decreased significantly (p< 0.001). The cholesterol/ SCBR ratio case children was also significantly high (p< 0.001) when compared with control children. The case and control children were also divided according to their sex [Table - 2]. Serum cholesterol level of male case children was found to be significantly high (p< 0.05) and SCBR level was significantly low (p< 0.001) and its ratio was significantly high (p< 0.001) when they were compared with male control children. There was no significant difference in the level of serum cholesterol of female case children but SCBR was found to be significantly low (p< 0.001) and its ratio was significantly high (p< 0.001) in female case children when their levels were compared with respective control [Table - 2]. Level of serum cholesterol of children of young patients was found to be significantly increased (p< 0.01) but insignificant difference was noticed in the level in children of old patients on comparison with that of control children. Comparison of serum cholesterol level of children of young and old patients revealed significantly high level (p< 0.05) in children of young patient. SCBR level of children of young and old patients were found to be significantly low (p< 0.001) when they were compared with control children and comparison of SCBR levels of case children of young and old patients revealed significantly depressed level in children of young patients. The cholesterol/SCBR ratio of children of young and old patients were significantly high (p< 0.001) when compared with that of control children. When the ratio values of case children of young and old patients were compared with one another children of young patients revealed significantly (p< 0.001) high values [Table - 3]. These results revealed that there was greater risk of the disease in children of young patients. According to the age as well as sex of the patients, the case children were further grouped and compared with control children. Serum cholesterol level of case children of young male patients was found to be significantly elevated (p< 0.001) when they were compared with control children. Whereas comparison of serum cholesterol level of children of young female patients with control children and with children of young male patients revealed insignificant results. Comparison of SCBR levels of children of young male and young female patients with control children revealed significantly low (p< 0.001) values in case children of both groups. The SCBR level of children of young male patient was significantly low (p< 0.001) when they were compared with that of children of young female patients. Comparison of cholesterol /SCBR ratio of children of young male and young female patients with control children revealed significantly high (p< 0.001) values in case children of both groups. The ratio values of children of young male patients were also significantly high (p< 0.001) when compared with children of young female patients [Table - 4]. It was observed that paternal effect is dominant in young patients of MI. Comparison of serum cholesterol level of case children of old male and old female patients with control and with one another revealed insignificant results. SCBR levels and total cholesterol/SCBR ratio values were found to be significantly low (p< 0.001) and significantly high (p< 0.001) respectively in case children of old male and female patients when they were compared with control children. Further both levels were found to be significantly low (p< 0.001) and significantly high (p< 0.05) in children of old female patients when they were compared with that of children of old male patients [Table - 5]. This shows that maternal effect is dominant in old patients of MI. The case children were further grouped considering their sex as well as the age and sex of their parents. Serum cholesterol, SCBR and their ratio values of male children of young male and young female patients were compared with male control children and also with one another. Serum cholesterol levels of male case children of both groups rose significantly (p< 0.001) (p< 0.05) when they were compared with male control children but comparison of cholesterol level of case children of either group revealed in significant results. SCBR levels of male case children of young male and young female patients decreased significantly (p< 0.001) when they were compared with respective control. The level of SCBR of male children of young male patients was significantly lower (p< 0.001) than male children of young female patients. Cholesterol/SCBR ratio of male case children of young male and young female, patients was found to be significantly high (p< 0.001) when they were compared with that of male control children. The ratio value of male children of young male patients was also significantly higher (p< 0.001) than that of male children of young female patient [Table - 6]. The results suggest that father-son correlationship is stronger than mother-son correlation in young patients. When serum cholesterol level of female children of young male and young female patients was compared with respective control and also with one another it revealed insignificant results. In contrast SCBR levels of female case children of both groups decreased significantly (p< 0.001) when they were compared with female control children. Again the SCBR level of female case children of young male patients was significantly lower (p< 0.001) than that of female case children of young female patients. Cholesterol/SCBR ratio of female case children of young male and female patients was found to be significantly increased, (p< 0.001, (p 0.01) when creased, (p 0.001) (p< 0.01) when they were compared with that of female control children. The ratio value of female children of young male patients was also significantly higher (p< 0.001) than that of female children of young female patients [Table - 7]. Thus suggesting that father-daughter correlationship was stronger than mother-daughter correlation in young patients. Serum cholesterol and SCBR and Tc/ SCBR ratio levels of male children of old male and old female patients were compared with respective control children and also with one another. In this comparison serum cholesterol level of male case children of old male patients was only significantly elevated (p< 0.05) when they were compared with male control children, showing stronger father-son correlationship. In contrast studies on SCBR and Tc/SCBR proved mother-son correlationship to be stronger; therefore mother-son correlationship was considered to be stronger than father-son in old patients of MI [Table - 8] omparison of serum cholesterol of female children of old male and old female, patients with respective controls and with one another revealed insignificant results. SCBR levels of female case children of both groups decreased significantly (p< 0.001) and ratio values rose significantly (p< 0.01, p< 0.02) when they were compared with respective control but comparison of SCBR and ratio value of female case children of old male and old female patients resulted in significant difference so there was existence of both father-daughter and mother-daughter correlationship in old patients of MI and former correlationship is slightly stronger than latter [Table - 9].
This study pertains to the children of the age 1 to 20 years of patients of acute myocardial infarction. The level of serum cholesterol in female control children was higher than that of male control children but SCBR level in female control children was also considerably higher than that of male control children but SCBR level in female control children was also considerably higher than that of male children. The high level of serum cholesterol in females was balanced by its high level of SCBR. Our findings are in accord with Patterson and Slack.18 that females may be able to tolerate a raised cholesterol level better than males. In the study of patients of MI alongwith control, it was noticed that in some cases high serum cholesterol with proportionately high SCBR level showed no evidence of the disease whereas, proportionately lower SCBR even with low serum cholesterol level showed evidence of the disease. In the study of case children with control children, it was observed that in control group SCBR level rose with the increase in serum cholesterol level but this balance was not observed in the study of case children. Thus in case children the risk of the disease was more. Serum cholesterol level was slightly elevated in case children when they were compared with that of control children but the difference was not significant. The findings are in accord with many workers[1], [8], [11] but in contrast some studies[5], [6], [13], [15] reported significant increase in the level of serum cholesterol in case children. The level of serum cholesterol in children of young patients was significantly higher than that of children of old patients. Similar observations have been reported by many other workers.[4], [9], [17], [20] The SCBR level was laso found to be lower in case children, of young patients. Thus it was concluded that there was a greater risk of disease in children of patients having MI in young age. It was also observed that paternal effect is dominant in young and maternal effect is dominant in old patients of MI i.e. father-offspring correlationship is stronger in young and mother-offspring in old patients of MI. Some workers[6], [9] studied the serum cholesterol level in the children of men with premature MI and reported a significant father-offspring correlation-ship. In contrast many others[3], [14] studied intrafamilial association of serum cholesterol and triglyceride among related and unrelated house hold members and reported stronger mother-child correlationship than those for father-child but they were not significantly different. Our findings are in accord with two[21], [22] other studies who concluded that the relatives of younger men and older women dying of IHD had[5],[6],[7] fold increased risk of sudden death compared with general population. By the combined study1 of serum cholesterol and SCBR it was observed that the disease is more likely to transfer in male and its prevalence is also higher in male compared to female children. Forde and Thelle,[2] studied male population in the municipality of Tromso in N. Norway and found increased relative risk for CHD among 1st degree relatives of CHD cases. Wilson et al[14] confirmed the above observation. In contrast Mjos et al[14] concluded that there was no sex associated genetic influence for total cholesterol. To emphasize the genetic involvement an elaborate comparison was drawn. By the study of serum cholesterol in children of young patients of MI only father-son and mother-son correlationship appeared to exist; the former stronger than the latter but SCBR and Tc/SCBR ratio study showed that alongwith father-son and motherson correlationships there was existence of father-daughter and mother-daughter correlationships also. Among these correlations father-son and father-daughter correlationships are stronger than mother-son and mother-daughter respectively. Our results were in accordance with Phillips et al,[19] who reported that CHD aggregated in father-son pair in which the son has early onset of CHID. Aggregation is less clear among male sibs and is absent among mother-son pairs. Morrison et al,[15], [16] in a population survey reported that for father-son, mother-son, father-daughter and mother-daughter a positive significant correlationship existed of serum cholesterol level. In the old patients of MI, study on serum cholesterol showed only existence of father-son correlationship. In contrast, SCBR study showed existence of mother-son correlationship but Tc/SCBR ratio suggested existence of both father-son and motherson correlationships. It was also observed that mother-son is stronger than father-son correlationship. SCBR and ratio study also showed that father-daughter and mother-daughter correlationship was found to be equally significant. Garrison et al3 reported that both maternal and paternal cholesterol levels made an independent contribution to the prediction of the offsprings cholesterol, the mother's contribution was significantly greater than the fathers for male offspring with a similar but less striking relationship for female offspring. The data support the hypothesis that process levels of circulating cholesterol and SCBR may offer a mechanism whereby family history can be associated with future coronary disease risk.
The authors gratefully acknowledge the Director General, Indian Council of Medical Research, for providing the funds to carry out this project.
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