March 10, 2014
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Large, small LDL diameters increased CV mortality risk

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Both large and small LDL particle diameters were independently associated with an increase in all-cause and cardiovascular mortality risk, with deaths from cardiovascular causes more highly associated with particle size than all-cause, researchers found.

“This study demonstrates that the mean particle diameter of LDL is associated with long-term total and cardiovascular mortality in patients undergoing coronary angiography, essentially independent of the main acknowledged cardiovascular risk factors,” Tanja B. Grammer, MD, of the Mannheim Institute of Public Health at the University of Heidelberg in Germany, and colleagues wrote. “Our results underline the impact of markers of the LDL metabolism on clinical endpoints beyond elevated LDL-C concentration.”

Study participants included 1,643 patients who were referred to coronary angiography but not prescribed lipid-lowering drugs. The participants were followed for a median follow-up of 9.9 years. During that time, 398 patients died, 246 of whom died of CV causes. The researchers used the composition of LDL obtained by beta-quantification to calculate the average particle diameters of the LDL.

The researchers found that, in patients undergoing coronary angiography, the mean particle diameter of LDL was associated with long-term total and CV mortality, stratifying patients with large (>16.8 nm) and small (<16.5 nm) LDL particle diameters particularly at risk vs. patients with intermediate diameters (16.5-16.8 nm) having the lowest risk. This finding was robust, even when adjustments were made for age and sex as well as an additional adjustment for other CV risk factors.

All-cause mortality HRs of the fully adjusted model were 1.71 (95% CI; 1.31-2.25) and 1.24 (95% CI; 0.95-1.63) for large and small LDL, respectively, and CV mortality showed comparable results.

An unexpected finding also raised questions about inflammatory markers and the associated risk. “The concentrations of inflammatory markers such as [C-reactive protein] and [interleukin-6] were highest in patients with buoyant LDL,” the researchers wrote. “The significance of this unexpected finding, however, remains elusive at this time. In particular, it is hard to decide whether systemic inflammation causes the accumulation of buoyant LDL or whether these lipoproteins are themselves responsible for the inflammatory reaction.”

Disclosure: The researchers report no relevant financial disclosures