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Shinji Koba, Yuuya Yokota,
Tsutomu Hirano,
Yasuki Ito,
Yoshihisa Ban,
Fumiyoshi Tsunoda,
Takatoshi Sato,
Makoto Shoji,
Hiroshi Suzuki,
Eiichi Geshi,
Youichi Kobayashi,
Takashi Katagiri
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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.
Journal of atherosclerosis and thrombosis 11/2008; 15(5):250-60. · 2.69 Impact Factor
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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.
12/2007: pages 115-123;
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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.
Atherosclerosis 12/2006; 189(1):206-14. · 3.79 Impact Factor
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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.
Circulation Journal 05/2006; 70(4):393-401. · 3.77 Impact Factor
