[Show abstract][Hide abstract] ABSTRACT: Recent evidence suggests that small dense low-density lipoprotein (sd-LDL) particles are more atherogenic than large-LDL in spite of their lower cholesterol content. This study aimed to determine whether sd-LDL-cholesterol (sd-LDL-C) is superior to LDL-C as a biomarker of coronary heart disease (CHD).
LDL particle size determined by gradient gel electrophoresis and sd-LDL-C concentrations quantified by heparin-magnesium precipitation were compared between 482 stable CHD patients and 389 non-diabetic subjects without CHD who were not receiving any lipid-lowering drugs.
Both male and female CHD patients had significantly smaller LDL particles and lower large-LDL-C concentrations (estimated by subtracting the sd-LDL-C concentration from the LDL-C concentration), and significantly higher sd-LDL-C concentrations than the control subjects. LDL-C concentrations were modestly higher and sd-LDL-C concentrations were significantly higher in 258 patients with angiographically documented severe CHD than in the patients with mild CHD irrespective of treatment by LDL-lowering drugs and history of myocardial infarction and/or coronary revascularization. Large-LDL-C concentrations, in contrast, were similar between the two groups. Multivariate logistic regression analysis revealed that sd-LDL-C levels were significantly associated with severe CHD independently of LDL-C.
sd-LDL-C levels are more powerful than LDL-C levels for the determination of severe stable CHD.
No preview · Article · Nov 2008 · Journal of atherosclerosis and thrombosis
[Show abstract][Hide abstract] ABSTRACT: Interleukin-6 (IL-6) and metalloproteinases (MMPs) are involved in the instability of vulnerable plaque associated with the induction of acute myocardial infarction (AMI). We examined the regional changes of cytokines, MMPs and adhesion molecules in patients with AMI to elucidate how these factors are involved in the onset of AMI.
One hundred and twenty-two patients with AMI were included. Blood was aspirated from the culprit coronary artery with a thrombectomy catheter, and was also sampled from peripheral veins during the coronary intervention. Control samples were obtained from the peripheral blood of age-matched patients.
The serum levels of IL-6 (P < 0.05), tumour necrosis factor-alpha (P < 0.005), MMP-1 (P < 0.001), MMP-13 (P < 0.001), soluble intercellular adhesion molecule-1 (P < 0.005), and soluble vascular cellular adhesion molecule-1 (P < 0.05) in peripheral blood were significantly higher in the AMI group than in the controls. Aspirated serum contained significantly higher levels of IL-6 (P < 0.001), MMP-1 (P < 0.001), and MMP-13 (P < 0.05) compared to the peripheral blood of AMI. Serum IL-6 levels were significantly higher in the aspirated than in the peripheral blood in the patients hospitalized within 6 h and 6-12 h, but were similar in the aspirated and peripheral blood of the patients hospitalized 12-24 h after the onset of AMI. There were no differences between the aspirated serum and peripheral blood in the levels of interleukin-1beta and MMP-2.
The levels of MMP-1, MMP-13 and IL-6 were higher in the culprit coronary artery than in the peripheral blood. These factors appear to be involved in the early stage of AMI.
No preview · Article · Mar 2008 · European Journal of Clinical Investigation
[Show abstract][Hide abstract] ABSTRACT: Recent evidence suggests that small dense low-density lipoprotein (sd-LDL) particles are more atherogenic than large-LDLs
in spite of their lower cholesterol contents. This study aimed to determine whether sd-LDL-cholesterol (sd-LDL-C) is superior
to LDL-C as a biomarker of the severe coronary heart disease (CHD). We compared the LDL particle size by gradient gel electrophoresis
and sd-LDL-C concentrations quantified by heparin-magnesium precipitation in two groups: 482 consecutive patients with stable
CHD who had undergone coronary arteriography and 389 non-diabetic subjects without CHD who were not receiving any lipid-lowering
drugs. The LDL size, large-LDL-C (estimated by subtracting the sd-LDL-C concentration from the LDL-C concentration), and HDL-C
were significantly lower in the CHD subjects than in the healthy subjects, and the sd-LDL-C was significantly higher, in both
men and women. The LDL-C was modestly higher and the sd-LDL-C was significantly higher in 258 patients with coronary events
(defined as coronary revascularization therapy) than in the patients without events, irrespective of treatment by LDL-lowering
drugs. Large-LDL-C, in contrast, was similar between the two groups. Multivariate logistic regression analysis revealed that
sd-LDL-C levels were significantly associated with coronary events independently of LDL-C, HDL-C, and high-sensitivity CRP.
The sd-LDL-C levels are more powerful than LDL-C levels as disease markers for the determination of high-risk patients among
patients with stable CHD.
[Show abstract][Hide abstract] ABSTRACT: Low-density lipoprotein (LDL) particles are heterogeneous with respect to their size, density, and lipid composition, and
the size of LDL particles is chiefly determined by their lipid contents. Small dense LDL particles have been suggested to
be highly atherogenic compared to large buoyant LDL. Our case-control studies have shown that the LDL particle size determined
by gradient gel electrophoresis was remarkably smaller in patients with coronary heart disease (CHD), irrespective of the
presence of diabetes and the differences in clinical situation and severity of CHD. In addition, small dense LDL-cholesterol
concentration evaluated by heparin magnesium precipitation was significantly higher in severe stable CHD and acute coronary
syndrome compared with non-CHD subjects and patients with mild CHD, while large LDL-cholesterol estimated by subtracting the
small dense LDL-cholesterol concentration from the LDL-cholesterol concentration, were somewhat lower in stable CHD compared
with healthy subjects. Further more, reduced LDL particle size and elevated small dense LDL-cholesterol levels were significantly
associated with metabolic dyslipidemia in Metabolic syndrome. These suggest that the predominance of small dense LDL and high
levels of small dense LDL-cholesterol are very promising risk marker for CHD.
[Show abstract][Hide abstract] ABSTRACT: Recent evidence suggests that decreased levels of adiponectin and elevated levels of C-reactive protein (CRP) and small, dense low-density lipoprotein cholesterol (sd-LDL-C) may be risk factors for the development of coronary heart disease (CHD) . This study sought to determine how these factors are associated with coronary events compared with LDL-C, an established potent risk factor, in stable CHD. LDL particle size, sd-LDL-C (assessed by the heparin-magnesium precipitation method), CRP, highmolecular weight adiponectin, apolipoproteins and hemoglobin A1c were compared among 219 stable CHD patients who had undergone coronary arteriography and 159 hypertensive patients without diabetes or CHD. None of the subjects received lipid-lowering drugs during the study. A coronary event was defined as a revascularization procedure within 6 months of blood measurement. Fasting LDL-C, sd-LDL-C, apolipoprotein B, hemoglobin A1c, and CRP were significantly higher in the patients with coronary events than in those without events. High-density lipoprotein cholesterol, apolipoprotein A-1 and adiponectin were significantly lower in the patients with coronary events than in those without events. LDL-C levels were similar between the non-CUD hypertensives and the CHD patients with events. Elevated sd-LDL-C was the only parameter found to be significantly associated with severe CHD independent of LDL-C, high-densty lipoprotein cholesterol, apolipoprotein B, adiponectin and CRP by multiple logistic regression analysis. These results suggest that sd-LDL-C is superior to LDL-C and adiponectin for predicting the progression of stable CHD.
[Show abstract][Hide abstract] ABSTRACT: We have investigated the clinical significance of small dense low-density lipoprotein-cholesterol (sd-LDL-C) concentrations in coronary heart disease (CHD). We measured the LDL size by gradient gel electrophoresis and quantified sd-LDL-C concentrations by a newly developed rapid assay using heparin-magnesium precipitation in 225 consecutive CHD patients without any lipid-lowering medication and 142 healthy middle-aged subjects as controls. The LDL size was markedly smaller and sd-LDL-C levels were significantly higher in CHD patients than in controls of both sexes, whereas LDL-C levels were comparable between CHD and controls. The LDL-C levels were significantly higher in a subpopulation of 84 patients with acute coronary syndrome than in other patients groups, while LDL size and high-density lipoprotein-cholesterol (HDL-C) were not found to vary among the patients. The sd-LDL-C increased as the number of diseased vessels or Gensini atherosclerosis score increased. Among the 123 stable CHD patients, multiple logistic regression analysis revealed that sd-LDL-C levels were significantly associated with the clinically severe cases requiring coronary revascularization independently of LDL-C, HDL-C and apolipoprotein B. The sd-LDL mass plays a more important role in the progression of CHD than the LDL size, and the sd-LDL-C concentration serves as a powerful surrogate marker for the prevention of CHD.
[Show abstract][Hide abstract] ABSTRACT: Although small dense low-density lipoprotein (sd-LDL) has an established association with diabetic dyslipidemia, previous studies have failed to show an association between sd-LDL and diabetes among coronary heart disease patients. This study investigated the prevalence of sd-LDL and abnormal glucose regulation in acute coronary syndrome (ACS).
LDL size at the onset of ACS was measured by nondenatured gradient gel electrophoresis in 314 of 429 consecutive patients. Sd-LDL was prevalent in 54% of the patients, irrespective of the presence of previously known diabetes (50% vs 60% in nondiabetes and diabetes, respectively). Diabetes was present in 122 (28%) of the patients, and 110 patients without diabetes underwent an oral glucose tolerance test. Impaired glucose tolerance (IGT) and newly detected diabetes were found in as many as 44% and 22% of the patients tested, even though their hemoglobinA1c levels were in the normal range (5.3+/-0.5%). The prevalence of sd-LDL was significantly higher in patients with glucose intolerance than in those with normal glucose tolerance (61% vs 42%).
IGT and diabetes were far more common than normal glucose regulation in ACS patients, and the abnormal glycometabolism was closely associated with highly atherogenic sd-LDL.
No preview · Article · May 2006 · Circulation Journal