Low-Density Lipoprotein Particle Diameter and Mortality: The Ludwigshafen Risk and Cardiovascular Health Study

Study Questions:

Are differences in the average diameter of low-density lipoprotein (LDL) particles associated with total and cardiovascular mortality?

Methods:

Data from the LURIC (Ludwigshafen Risk and Cardiovascular Health) study were used for the present analysis. The LURIC study is an ongoing cohort of 3,316 patients referred for coronary angiography, recruited between June 1997 and May 2001. Patients on lipid-lowering therapies were excluded in this study. Average particle diameter of LDL was calculated by β-quantification. The primary outcomes were total mortality and cardiovascular mortality.

Results:

A total of 1,643 patients were included in this study. Patients with small LDL were on average younger than those with large or intermediate LDL. Current or past smoking, diabetes mellitus, and hypertension were more prevalent among patients with small LDL. There was no obvious association of LDL size with angiographic coronary artery disease. Over a median follow-up of 9.9 years, 398 patients died, of which 246 died of cardiovascular causes. Patients with LDL with intermediate average diameters (16.5-16.8 nm) were used as reference category. Compared to this group, patients with large particles (>16.8 nm) had an increased risk for all-cause mortality after adjustment for cardiovascular risk factors (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.31-2.25). Those with small LDL particles (16.5 nm) also had increased risk for mortality, which did not reach statistical significance (HR, 1.24; 95% CI, 0.95-1.63). When just cardiovascular disease mortality was considered, both large particles and small particles were associated with increased risk (HR, 1.89; 95% CI, 1.32-2.70 for large LDL particle size and HR, 1.54; 95% CI, 1.06-2.12 for small LDL particle size). Patients with large LDL had higher concentrations of the inflammatory markers interleukin (IL)-6 and C-reactive protein than patients with small or intermediate LDL.

Conclusions:

The investigators concluded that calculated LDL particle diameters identify patients with different profiles of LDL subfractions. Both large and small LDL diameters are independently associated with increased risk of mortality from all causes and, more so, due to cardiovascular causes compared with LDL of intermediate size.

Perspective:

These data suggest that continued examination of LDL particle size related to outcomes is warranted. Perhaps mean diameter is a clinically useful tool when measuring lipids. However, looking at mean particle diameter in additional and multi-ethnic cohorts is an important next step.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Hypertension, Smoking

Keywords: Lipoproteins, LDL, Coronary Artery Disease, Dyslipidemias, C-Reactive Protein, Interleukin-6, Cardiovascular Diseases, Risk Factors, Hypertension, Diabetes Mellitus, Smoking


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