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This study supports the use of non-HDL cholesterol as the more practical …

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- The atherogenic and metabolic impact of non-HDL cholesterol versus other lipid sub-components among non-diabetic and diabetic Saudis

Grundy, in a recent report, emphasizes that there has to be strong evidence of superiority for non-HDL cholesterol to be regarded as the primary target of lipid therapy [6]. Since then, clinical trials all over the world have made further contributions in the challenge to discover whether non-HDL cholesterol is indeed superior to the incumbent LDL cholesterol as the primary target of lipid-lowering therapy [7-10]. This study can be regarded as contributing to this growing evidence, using Saudis as the first subjects to be considered in the Arab population as a whole.

The superiority of non-HDL cholesterol over LDL-cholesterol started from a comparison of equations; non-HDL cholesterol is a simple subtraction while LDL-cholesterol is derived from 3 different analytes, with a conversion factor assumption. From a practical point of view, it is easier and faster to compute for non-HDL cholesterol not to mention the unreliability of LDL-cholesterol values when ≥ 400 mg/dl of serum triglycerides is reached [11]. Arguably, LDL cholesterol remains to be the major player in atherogenesis, but, when inaccuracy sets in, the validity of clinical management will also be open to question. Several studies support the view that non-HDL cholesterol and apo B are superior to LDL cholesterol, especially among diabetics whose triglyceride levels exceed the accuracy limit of the Friedewald formula for LDL-cholesterol [11,12].

A study by Liu and his colleagues concludes that non-HDL cholesterol is a stronger predictor of CHD death among those with diabetes than among those with LDL cholesterol and should be given more consideration in the clinical approach to risk reduction among diabetic patients [8]. Contrary to their findings, our study suggests non-HDL as a stronger predictor among non-diabetics rather than diabetics, in terms of developing CHD. The difference in results can be explained by several factors. First among these factors is the choice of dependent variable and the number of samples used; their study utilized CHD death as the dependent variable with 19,381 samples while our study focused more on existing CHD as the dependent variable with 733 samples. The great discrepancy in sample size and the unequal distribution of non-diabetics (462) to diabetics (271) in the present study may also have contributed to the disagreement between the findings. Nevertheless, the potential significance of non-HDL as a clinical tool in the management of non-diabetic patients merits supplementary investigation. Furthermore, in their report there is a negative association of HDL with CHD, which is different from our results. This could be explained by the fact that Arabs, Saudis in particular, have a lower prevalence of hypercholesterolemia than do their American and European counterparts [13]. In addition, we also considered the younger population used, together with the culture and lifestyle differences, one of which is the total prohibition of alcoholic beverages in the Kingdom, which can greatly alter the lipid and coagulation profiles of the subjects used [14,15]. As evidenced by the results of this study, decreased HDL-cholesterol levels may not be as powerful as the rest of their lipid counterparts when it comes to predicting CHD, but its contribution to the progression of diabetes mellitus and metabolic syndrome in the Saudi population is nevertheless equally important.

In our study, elevated triglycerides were the consistent single significant contributor to the development of CHD, diabetes mellitus and metabolic syndrome among the rest of the lipid sub-components. While it is apparent that hypertriglyceridemia is more closely linked to the constellation of abnormalities which constitutes metabolic syndrome, the exact atherogenic properties of triglycerides have been hard to explain, perhaps secondary to the greater biologic variance than cholesterol [16]. Williams and his colleagues report that elevated triglycerides is a common abnormality in patients who had myocardial infarction [17], while Benfante confirm that triglyceride value in those below 60 years was an independent predictor of CHD, but not in older people [18]. The mean age of our subjects fall within the cut-off set by the latter's study, which probably explains why triglycerides played a significant part in the pathogenesis of these chronic diseases. The association of triglycerides with coronary heart disease remains difficult to unravel. Elevated levels do not necessarily indicate increased atherogenicity suggesting that only certain components may be atherogenic or may be associated with metabolic abnormalities which are atherogenic [16].

This study measured the lipid profiles of non-diabetic and diabetic Saudi subjects to assess the impact of individual lipid parameters, as compared to non-HDL cholesterol, in predicting coronary heart disease. Given the fact that non-HDL cholesterol possesses all the atherogenic lipoproteins (VLDL, intermediate-density lipoprotein and LDL) as opposed to LDL alone [8], the possibility that it is superior to LDL in CHD risk prediction is undoubtedly strong. Coronary heart disease is the end product of a chronic interplay of metabolic and environmental influences requiring the element of time, which is not modifiable. Early detection and intervention, therefore, using clinically important parameters such as non-HDL cholesterol are vital to overall success in the management of CHD.

This study acknowledges some limitations. The significant age gap in this study aside from the co-existing morbidity which is diabetes, has undoubtedly contributed much of the difference in relative risks of both the non-diabetic and diabetic subjects. Other confounding factors in the development of CHD which were not controlled in this study, such as smoking, the presence of hypertension, obesity, gender and family history warrant additional investigation. Nevertheless, this study acknowledges the fact that lipids play an essential role in atherogenesis, and that it is accelerated in patients with diabetes mellitus. It is the authors' hope that this study will be of help in the future assessment of international authorities such as NCEP in acknowledging novel risk factors such as non-HDL cholesterol as a potent risk factor which should be emphasized in the prevention of coronary heart disease through lipid lowering agents.

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