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Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) plasma populations are composed of heterogeneous subfractions that are different in size, density and protein/lipid content. There is increasing evidence that small, dense LDL particles are strongly associated with higher cardiovascular disease risk. Similarly, several studies have investigated whether smaller HDL particles are more protective than their larger counterparts and more recent findings suggest that small, dense HDL has significantly higher atheroprotective activity than larger L HDL. Yet, certain impairments of the protein/lipid content in small, dense HDL may decrease its antiatherogenic capacity or even induce pro-atherogenic properties. Therefore, it seems that the small, dense phenomenon applies to both LDL and HDL particles. Measurement of LDL and HDL cholesterol concentrations has proven clinical utility, while the usefulness of LDL and HDL subclasses determination in clinical practice offers grounds for further exploration. However, LDL and HDL particles characterisation requires either special equipment or a lengthy analytical time and is, therefore, still unsuitable for general clinical use. It remains to be established whether lipoprotein subclasses should be analyzed in routine practice, although their assessment in high-risk subjects could be recommended. (Clin. Lab. 2009;55:421-429)

Background: Increasing evidence suggest that the ‘quality’ rather than only the ‘quantity’ of low-density lipoprotein (LDL) exerts a great influence on the cardiovascular risk. Small, dense LDL seem to be an important predictor of cardiovascular events and progression of coronary artery disease (CAD) and their predominance has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. Discussion: Some studies showed in past years that small, dense LDL are usually elevated in patients at very high cardiovascular risk, such as those with CAD and type 2 diabetes. More recently elevated levels of these particles have been found in other categories of patients at high cardiovascular risk, such as those with non-coronary forms of atherosclerosis (e.g. with carotid artery disease, aortic abdominal aneurysm and peripheral arterial disease) and metabolic diseases (with polycystic ovary syndrome and growth hormone deficiency); notably, in most of them, the predominance of small, dense LDL characterised their type of dyslipidaemia, alone or in combination with elevated triglycerides and reduced high-density lipoproteins cholesterol concentrations. Conclusions: The therapeutical modulation of small, dense LDL have been shown to significantly reduce cardiovascular risk and weight reduction and increased physical activity may constitute first-line therapy. In addition, lipid-lowering drugs are able to favourably alter these particles and fibrates and nicotinic acid seem to be the most effective agents. Promising data are also available with the use of rosuvastatin, the latest statin introduced in the market, and ezetimibe, a cholesterol absorption inhibitor

Low density lipoproteins (LDL) comprise in humans two different main fractions: large, buoyant and small, dense particles. Small, dense LDL particles correlate negatively with plasma HDL levels and positively with plasma triglyceride concentrations and are associated with the metabolic syndrome and increased risk for cardiovascular disease. LDL size seems to be an important predictor of cardiovascular events and progression of coronary heart disease (CHD). In addition, several studies have suggested that therapeutic modulation of specific LDL subclasses may be of great benefit in reducing the atherosclerotic risk. Therefore, LDL size measurement may be of potential value in the clinical assessment and management of patients at high risk of CHD, a category that comprises individuals with non-coronary forms of atherosclerosis: peripheral arterial disease, carotid artery disease, abdominal aortic aneurysm. Potentially, screening for the presence of small, dense LDL in patients with those clinical forms of atherosclerosis may identify those with even higher vascular risk and may contribute in directing specific anti-atherosclerotic treatments in order to prevent new vascular events in the same or another district. However, to-date, not so many studies have investigated the LDL size in patients with non-coronary forms of atherosclerosis and we need to wait for further contributions with larger number of patients, even if available data seem to suggest an association between small, dense LDL and such diseases. The predominance of small dense LDL particles has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III but screening for the presence of small, dense LDL particles in patients with non-coronary forms of atherosclerosis has not been so far recommended