**Author details**

132 Lipoproteins – Role in Health and Diseases

can already now be used in clinical settings.

that conventional risk factors plus LDL-C, and possibly one more risk factor, is enough as tools for prediction of risk – a very conservative approach which is so (too!) common in US! How much do confounders/risk factors impact on the results from all these CV risk studies? Importantly, in ERFC (10) and also in the majority of studies cited above, the impact of adjusting for major confounders was very small and only changed the risk (HR, RR or OR) to a minor degree. In fact, the apolipoproteins added value, measured as net reclassification index (NRI) in several large studies (88,91,170). This indicates that apolipoproteins, especially the apo-ratio, could change the numbers of individuals either to a higher or a lower CV risk compared to conventional lipids. Newly developed risk algorithms based on the apo-ratio have also been developed showing at least equal predictive or even better values than conventional risk algorithms (102,117,118). Thus, apoB, apoA-I and the apo-ratio

In the present review the apo-ratio has been shown to be closely related to many different types of CV events in prospective studies. These common diseases are myocardial infarction, stroke, especially ischemic stroke, heart failure, renal failure, aortic aneurysms, development of diabetes, including retinopathy **(Table 3 I and II)**. However, in the metaanalyses published so far only CV events have been chosen as endpoints and other

Is the apo-ratio useful in predicting various metabolic and inflammatory conditions commonly underlying atherosclerosis and its future consequences? In fact, the apo-ratio has also been found to be a valuable summarizing index of lipid-abnormalities and their complications in a large number of studies of the MetS and/or diabetes (125-139,143,144). In addition, the apo-ratio values are also increased in patients with hypertension, obesity, in pubertal children and in those with heredity for CV diseases (130,141). The apo-ratio is also more closely than lipids related to atherosclerosis in a large number of studies in which different techniques like coronary angiography, arterial wall thickness obtained by ultrasound techniques in the carotid arteries (CIMT values) or even in the coronary arteries by intravascular ultrasound (IVUS) and arterial abnormalities such as the endothelial dysfunction have been used (145-162). Thus, in all these disease or risk situations the aporatio may identify those at an increased risk even better than what is currently performed by

The newest research data on the apo-ratio have not yet been reviewed by international guideline committees. Thus, so far, in the newest guidelines developed over the last few years non-HDL-C and apoB are mentioned, and accepted for clinical use, whereas the apo-

In conclusion; with all the new knowledge presented in this paper about the strong relations between apoB, apoA-I, and the apo-ratio, and CV risk as well as other disease manifestations, it is proposed, as many researchers have already done, that these strong risk predictors/factors/markers are included in new guidelines. In many disease conditions and manifestations of atherosclerosis apolipoproteins are at least equally informative, and often better than LDL-C, non-HDL-C and lipid ratios in predicting risk. It is realized that there

manifestation of CV risk related to atherosclerosis have been excluded.

using LDL-C or the recently recommended non-HDL-C.

ratio is still waiting for acceptance (9,35,178,179).

Göran Walldius *Department of Epidemiology, Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden* 
