Increased Small Low-Density Lipoprotein Particle Number

Abstract

Background-Levels of LDL cholesterol (LDL-C) are frequently not elevated in individuals with the metabolic syndrome (MetSyn). However, the atherogenic potential of LDL may depend on the number and size of LDL particles in addition to the cholesterol content of LDL. Methods and Results-We examined the sex-specific cross-sectional relations of small LDL particle number (determined by nuclear magnetic resonance spectroscopy) to the presence of MetSyn and its components in 2993 Framingham Heart Study participants (mean age, 51 years; 53% women) without cardiovascular disease (CVD) and the relations of small LDL particle number to CVD incidence in people with MetSyn. The MetSyn (Ն3 of 5 traits as defined by the National Cholesterol Education Adult Treatment Panel III) was present in 27% of men and 17% of women. In both sexes, small LDL particle number increased from 0 to 5 MetSyn traits, a pattern partly accounted for by strong correlations between small LDL particle number and serum triglycerides (rϭ0.61, PϽ0.0001) and HDL-C (rϭϪ0.55, PϽ0.0001). Compared with participants without the MetSyn, those with the MetSyn had a higher CVD event rate. However, among participants with the MetSyn, CVD rates were similar for groups with an elevated versus a lower number of small LDL particles (defined by the sex-specific median). Conclusions-Small LDL particle number is elevated in the MetSyn, increases with the number of MetSyn components, and most prominently is correlated with triglycerides and HDL-C. Whereas increased small LDL particle number identified the MetSyn with high sensitivity, a higher small LDL particle number was not associated with greater CVD event rates in people with the MetSyn.

Lipid metabolism in long-lived families: the Leiden Longevity Study

“…Thus, people with a small mean LDL particle size have relatively more small LDL particles as compared with people with a large mean LDL particle sizes. Small LDL particle sizes are associated with type II diabetes (Festa et al 2005), metabolic syndrome (Gentile et al 2008;Kathiresan et al 2006), insulin resistance (Garvey et al 2003;Goff et al 2005), incident CVD (Mora et al 2009), and future CAD (El Harchaoui et al 2007). Possible atherosclerosis could be induced by those small LDL particles, as indicated in a study of two knockout mice strains with similar cholesterol levels, were the Ldr −/− Apob 100/100 mice had a larger number (Veniant et al 2008).…”

Association of hypertension with small, dense low-density lipoprotein in patients without metabolic syndrome

“…In MS, the mechanism for sdLDL formation is known to be related to IR and hypertriglyceridemia; this relationship was demonstrated in the Framingham Heart study. 18 Diabetes, MS, and IR all have associated atherogenic lipids, including a predominance of sdLDL, lower HDL cholesterol, and higher TG levels. [26][27][28] Goff et al 29 reported that IR was associated with increased numbers of sdLDL particles in the Insulin Resistance Atherosclerosis Study.…”

“…30 Most of these conditions are frequently associated with HTN, but the exact role of HTN in sdLDL formation is still obscure. Systolic blood pressure and DBP were significantly correlated with small LDL particle numbers in patients with MS. 18 Several studies reported the association of HTN with an elevation of sdLDL levels. Landray et al 31 reported a preponderance of smaller LDL subfractions in patients with untreated HTN, but the study population did not completely exclude patients with MS or hypertriglyceridemia.…”

“…16,17 In the Framingham Heart Study, both men and women with MS had a higher number of small LDL particles. 18 HTN is also a component of MS. In the Framingham Heart Study, patients with MS had systolic and diastolic blood pressures (DBPs) that were significantly correlated with small LDL particle number.…”

“…In the Framingham Heart Study, patients with MS had systolic and diastolic blood pressures (DBPs) that were significantly correlated with small LDL particle number. 18 Although the roles of both insulin resistance and hypertriglyceridemia on the formation of sdLDL are well studied, few studies regarding the contribution of HTN to sdLDL formation have been published. Furthermore, the relationship between HTN and sdLDL is not well understood in patients without MS.…”