Lipoprotein remnants and dense LDL are associated with features of unstable carotid plaque: A flag for non-HDL-C
Introduction
The degree of carotid artery stenosis has long been considered the most reliable predictor of stroke-risk in patients with carotid artery disease. However, factors other than the degree of stenosis determine whether a carotid plaque will result in acute neurologic events or not, in particular the presence of a vulnerable plaque [1], [2]. While LDL-C is a strong risk factor for coronary events, the association is definitely weaker when the focus is on cerebrovascular events. Despite the inconsistent association between cholesterol levels and the risk of stroke, statin therapy, the mainstay LDL-C lowering approach, is associated with a significant reduction of stroke incidence in both primary and secondary prevention [3]. Although these data do not support a role of LDL-C as risk factor for ischemic stroke, they also leave plausible the contribution of LDL-C independent, anti-inflammatory mechanisms of statins on plaque stability [4]. On the other hand, recent trials based on drugs that raise HDL-C have failed in preventing “hard” endpoints [5] and genetic studies have found that higher HDL-C due to known genetic polymorphisms are not associated to a decreased risk of myocardial infarction [6]. Finally, there is evidence that quality (i.e. size and density) of LDL particles rather than their plasma concentration may play a role in modulating atherosclerotic plaque cellular composition and stability [7], [8].
Here we present novel data on the potential contribution of each single lipoprotein subclass, including dense LDL and triglycerides-rich lipoprotein remnants as compared to standard components of the lipid profile, on cellular composition of carotid plaques retrieved from patients undergoing endarterectomy [9].
Section snippets
Patients
We studied 45 consecutive patients, undergoing endarterectomy for significant narrowing (>70%) of the internal carotid artery. The specimens of primary lesion retrieved at surgery were immediately placed in an optimal cutting temperature compound (OCT compound), frozen in liquid nitrogen and stored at −80 °C as previously described [9]. At the time of endarterectomy, all patients were already taking anti-platelet therapy (acetylsalicylic acid 100 mg/day), and 9 out of 45 patients were on
Results
The 45 patients (35 males, 10 female) were aged 68 ± 8 years. Plasma lipoprotein profile at the time of surgery was characterized by plasma total cholesterol concentration of 233 ± 37 mg/dl, LDL-C 153 ± 35 mg/dl, HDL-C 53 ± 14 mg/dl, non-HDL-C 180 ± 39 mg/dl, triglycerides (TG) 144 ± 61 mg/dl, Lp(a) 22 ± 22 mg/dl. The cholesterol distribution across lipoprotein density range is presented in the panel A of the Fig. 1. Lipoprotein (a) density range overlaps with the densest LDL particles
Discussion
This study, for first the first time, provides evidence of a direct association between carotid macrophage content, a marker of unstable plaque, and cholesterol carried in the dense LDL particles and in the TG-rich IDL and VLDL. Moreover, we confirmed the pathophysiological relevance of the non-HDL-C as compared to the routine lipid parameters in accounting for the inflammatory cellular component of the carotid plaque.
The causal relationship between cholesterol levels and stroke is complex and
References (16)
- et al.
Association between the --514 c-->t polymorphism of the hepatic lipase gene promoter and unstable carotid plaque in patients with severe carotid artery stenosis
J Am Coll Cardiol
(2002) - et al.
Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention
Lancet Neurol
(2009) - et al.
Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study
Lancet
(2012) - et al.
Common hepatic lipase gene promoter variant predicts the degree of neointima formation after carotid endarterectomy: impact of plaque composition and lipoprotein phenotype
Atherosclerosis
(2006) - et al.
Susceptibility of small, dense low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B
Am J Med
(1993) - et al.
Small dense LDL and VLDL predict common carotid artery IMT and elicit an inflammatory response in peripheral blood mononuclear and endothelial cells
Atherosclerosis
(2009) - et al.
Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke
J Am Med Assoc
(2004) - et al.
Statin treatment and carotid plaque composition. Review of clinical studies
Curr Vasc Pharmacol
(2012)