The small, dense LDL phenotype and the risk of coronary heart disease: epidemiology, patho-physiology and therapeutic aspects.

Department of Food Sciences and Nutrition, Laval University, Ste-Foy, Québec, Canada.
Diabetes & Metabolism (Impact Factor: 2.85). 10/1999; 25(3):199-211.
Source: PubMed

ABSTRACT More than decade ago, several cross-sectional studies have reported differences in LDL particle size, density and composition between coronary heart disease (CHD) patients and healthy controls. Three recent prospective, nested case-control studies have since confirmed that the presence of small, dense LDL particles was associated with more than a three-fold increase in the risk of CHD. The small, dense LDL phenotype rarely occurs as an isolated disorder. It is most frequently accompanied by hypertriglyceridemia, reduced HDL cholesterol levels, abdominal obesity, insulin resistance and by a series of other metabolic alterations predictive of an impaired endothelial function and increased susceptibility to thrombosis. Whether or not the small, dense LDL phenotype should be considered an independent CHD risk factor remains to be clearly established. The cluster of metabolic abnormalities associated with small, dense LDL particles has been referred to as the insulin resistance-dyslipidemic phenotype of abdominal obesity. Results from the Québec Cardiovascular Study have indicated that individuals displaying three of the numerous features of insulin resistance (elevated plasma insulin and apolipoprotein B concentrations and small, dense LDL particles) showed a remarkable increase in CHD risk. Our data suggest that the increased risk of CHD associated with having small, dense LDL particles may be modulated to a significant extent by the presence/absence of insulin resistance, abdominal obesity and increased LDL particle concentration. We suggest that the complex interactions among the metabolic alterations of the insulin resistance syndrome should be considered when evaluating the risk of CHD associated with the small, dense LDL phenotype. From a therapeutic standpoint, the treatment of this condition should not only aim at reducing plasma triglyceride levels, but also at improving all features of the insulin resistance syndrome, for which body weight loss and mobilization of abdominal fat appear as key elements. Finally, interventions leading to reduction in fasting triglyceride levels will increase LDL particle size and contribute to reduce CHD risk, particularly if plasma apolipoprotein B concentration (as a surrogate of the number of atherogenic particles) is also reduced.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: bstract:Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Obesity has been suggested as a major risk factor for this disease. This study aims to assess the relation between obesity and CAD in a selected group of Egyptian population. Other risk factors, including blood pressure, blood glucose, and lipids have also been investigated. The study included 80 patients with CAD (mean age: 47.86 years, males / females: 43/37),and 40 healthy controls (mean age: 46.15 years, males / females: 13/27). CAD patients were divided according to their body mass index (BMI) into 2 main groups: normal weigh group (BMI: 18.5–24.9, n=40) and abnormal weight group (BMI≥25, n= 40), the latter group was further sub-divided into overweight group (BMI: 25.0–29.9, n= 20) and obese group (BMI≥ 30, n= 20).The study revealed marked increase in systolic blood pressure (SBP), and diastolic blood pressure (DBP) among CAD patients compared to normal subjects. Significant increase in serum lipids [total cholesterol (TC), triglycerides (TGs), low density lipoprotein cholesterol (LDL-C)] and glucose, as well as blood glycosylated hemoglobin (HbA1c) % were also recorded. This goes in parallel with a reduction in high density lipoprotein cholesterol (HDL-C) and NO level in all CAD patients. However, these changes together seemed to be more drastic in the obese patients comparing with control and CAD patients with normal and overweight profile. So,it can conclude that obesity confers independent risk factor for CAD, probably through influencing interaction with the traditional risk factors, such as hypertension, dyslipidemia and hyperglycemia.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Familial combined hyperlipidaemia (FCHL) is a complex genetic disorder conferring high risk of premature atherosclerosis, characterized by high cholesterol and/or triglyceride, low high density lipoprotein (HDL) cholesterol and insulin resistance. We examined whether pioglitazone, added to conventional lipid-lowering therapy, would favourably affect metabolic parameters and alter body fat content. We undertook a randomized, double blind, placebo-controlled study in 22 male patients with FCHL treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, increasing to 45 mg for 12 weeks. Magnetic resonance imaging and proton magnetic resonance spectroscopy were performed to measure adipose tissue (AT) body content as well as intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) at baseline and after treatment. Significantly improved in the pioglitazone group were: triglyceride/HDL (atherogenic index of plasma) -32.3% (p=0.002), plasma glucose -4.4% (p=0.03), alanine-aminotransferase (ALT) -7.7% (p=0.005) and adiponectin 130.1% (p=0.001). Pioglitazone treatment resulted in a significant increase in total (5.3%, p=0.02) and subcutaneous (7.1%, p=0.003) adipose tissue as well as in soleus-IMCL levels (47.4%, p=0.02) without alteration in intra-abdominal AT or IHCL. Changes in ALT and AST and IHCL were strongly correlated (r=0.72, p<0.01; r=.0.86, p<0.01, respectively). In patients with FCHL on conventional lipid-lowering therapy, the addition of pioglitazone acts favourably on several metabolic parameters.
    Atherosclerosis 12/2007; 195(1):e181-90. DOI:10.1016/j.atherosclerosis.2007.03.043 · 3.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The cholesterol-raising potential of saturated fats has been noted for 50 years, but how they function and which among the saturated fats are most to blame is only now becoming apparent. The focus has shifted from saturated fats to individual fatty acids and the total composite of fatty acids (SFA, MUFA, PUFA) that comprise our daily fat intake. An adequate intake of both PUFA and SFA may be needed for the ideal LDL/HDL ratio in blood, as both contribute to the regulatory balance in lipoprotein metabolism. Palm oil, by virtue of its fatty acid composition equally balanced between saturated and unsaturated fatty acids, impacts blood lipids in different ways, depending on an individual's lipid profile. Recently, the realization that partially hydrogenated fats (containing trans fatty acids) have adverse health effects has necessitated finding alternative fat sources that provide specific functional characteristics without compromising health. The immediate solution would seem to be blending appropriate natural saturated and polyunsaturated fats to meet the combined requirements for food technology and energy metabolism. In technical situations where a higher-melting point fat is needed, as in margarines, shortenings, and frying oil, palm oil – or more specifically palm olein – would appear to be the fat of choice for blending with unsaturated oils.
    European Journal of Lipid Science and Technology 04/2007; 109(4):453 - 464. DOI:10.1002/ejlt.200700005 · 2.03 Impact Factor