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Dimensioni delle LDL e rischio cardiovascolare

Sotto la comune denominazione di LDL, definite come lipoproteine con una densità compresa tra 1.006 e 1.063, vengono incluse particelle che condividono la componente proteica (un'unica molecola di apo B-100), ma che si differenziano per un variabile contenuto in grassi, pur restando il colesterolo quello prevalente. Particelle dunque eterogenee per composizione, peso, densità e volume che possono essere suddivise in varie sottoclassi con opportune metodiche. Tutte le LDL, proprio in virtù del loro compito biologico di trasporto del colesterolo alla periferia, hanno un forte potere aterogeno, ma tra di esse alcune lo hanno di più e altre di meno. Le LDL piccole e dense da tempo sono considerate quelle più aterogene, forse perché entrano più facilmente negli spazi sub endoteliali, si legano meno facilmente ai recettori LDL, hanno un tempo di residenza in circolo più lungo ed una maggiore affinità per i proteoglicani. La Grammer e coll. confermano che le dimensioni delle LDL sono strettamente associate al rischio cardiovascolare, ma la relazione tra dimensioni delle LDL e rischio non è rettilinea. Il rischio è più basso per le LDL di dimensioni medie e più elevato per quelle di dimensioni minori o maggiori.

Low-density lipoprotein particle diameter and mortality: the Ludwigshafen Risk and Cardiovascular Health Study

Grammer TB, Kleber ME, März W, Silbernagel G, Siekmeier R, Wieland H, Pilz S, Tomaschitz A, Koenig W, Scharnagl H

Eur Heart J. 2014 Feb 25. [Epub ahead of print]

AIMS: The aim of the study was to examine whether differences in average diameter of low-density lipoprotein (LDL) particles were associated with total and cardiovascular mortality.
METHODS AND RESULTS: We studied 1643 subjects referred to coronary angiography, who did not receive lipid-lowering drugs. During a median follow-up of 9.9 years, 398 patients died, of these 246 from cardiovascular causes. We calculated average particle diameters of LDL from the composition of LDL obtained by ß-quantification. When LDL with intermediate average diameters (16.5-16.8 nm) were used as reference category, the hazard ratios (HRs) adjusted for cardiovascular risk factors for death from any cause were 1.71 (95% CI: 1.31-2.25) and 1.24 (95% CI: 0.95-1.63) in patients with large (>16.8 nm) or small LDL (<16.5 nm), respectively. Adjusted HRs for death from cardiovascular causes were 1.89 (95% CI: 1.32-2.70) and 1.54 (95% CI: 1.06-2.12) in patients with large or small LDL, respectively. 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. Equilibrium density gradient ultracentrifugation revealed characteristic and distinct profiles of LDL particles in persons with large (approximately even distribution of intermediate-density lipoproteins and LDL-1 through LDL-6) intermediate (peak concentration at LDL-4) or small (peak concentration at LDL-6) average LDL particle diameters.
CONCLUSIONS: Calculated LDL particle diameters identify patients with different profiles of LDL subfractions. Both large and small LDL diameters are independently associated with increased risk mortality of all causes and, more so, due to cardiovascular causes compared with LDL of intermediate size.

Eur Heart J. 2014 Feb 25. [Epub ahead of print]