Searching for new coronary heart disease risk factors.

with a relative risk of approximately 2·3 for development of ischaemic heart disease. Importantly these data also indicate a temporal relationship between elevated albumin excretion rate and subsequent cardiovascular disease events which was not confounded by the presence of previous clinically apparent ischaemic heart disease or diabetes. Although the increase in urinary albumin excretion is consistently accompanied by an increased capillary leakage of albumin in the whole body, the reasons for the increased cardiovascular risk in subjects with microalbuminuria are largely unknown. In diabetes, microalbuminuria is associated with an adverse lipid profile with evidence of generalized endothelial dysfunction and with insulin resistance, the latter of which have been suggested as potential mediators of both raised urine albumin excretion and cardiovascular disease. Insulin resistance has been associated with microalbuminuria in diabetic subjects, their relatives and non-diabetic subjects, and has recently been related to inflammatory markers, such as C-reactive protein. A strong relationship between C-reactive protein and the development of atherosclerotic disease has been observed in experimental and clinical studies. Very recently, a significant association between C-reactive protein and fibrinogen on the one hand, and albumin excretion rate in the microalbuminuric range on the other, has been described in Type 2 diabetic as well as non-diabetic individuals, suggesting that chronic inflammation could be a possible mechanism linking microalbuminuria and macrovascular disease. In a report from the Hoorn Study, a large population study of cardiovascular risk factors in the Netherlands, microalbuminuria and pre-existing atherosclerotic disease independently predicted cardiovascular and all-cause mortality, indicating that microalbuminuria affects mortality risk through a mechanism distinct from generalized atherosclerosis. This finding, though at variance with that of the MONICA Study, is in accord with the results of a cohort study of Type 2 diabetes, in which microalbuminuria not only predicted incident coronary heart disease, but was, in turn, predicted, in patients with a normal baseline albumin excretion rate, by pre-existing coronary heart disease. This suggested that microalbuminuria and atherosclerotic disease may not be causally related but rather reflect common determinants. It is possible therefore that, also in the general population, microalbuminuria, elevated levels of inflammatory proteins and atherosclerosis may See page 1922 for the article to which this Editorial refers