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: 3.27). 10/1999; 25(3):199-211.
Source: PubMed


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.

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    • "The causal association between obesity and elevated blood pressure has been demonstrated by large population based studies .The majority of patients with high blood pressure are overweight, and hypertension is about 6 times more frequent in obese subjects than in lean men and women (Rangaswamy et al., 1997). Dyslipidemia is also an important comorbidity of obesity associated with a very high incidence of coronary and vascular events (Lamarche et al.,1999).One study indicated that dyslipidemia of obesity is characterized by elevated TC, TGs , LDL-C and decreased HDL-C and that dyslipidemia is associated with increased risk of CAD (Walldius et al.,2001). In the present study, these relations have confirmed where CAD patients exhibited marked increase in serum TC, TGs, total lipid and LDL-C levels, which were significant when compared to control group. "
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    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.
    Full-text · Article · Jan 2012
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    • "Obesity was defined as BMI≥25 kg/m2, using body weight and height in all subjects, according to the Asian guideline, and central obesity was also defined as waist circumference ≥90 cm for men and ≥85 cm for women, defined in 2006 by Korean Society of Study of Obesity.18 We followed NCEP-ATP III Asian guideline19 components to define metabolic syndrome, which are consisted of central obesity (waist circumference≥90 cm for men and ≥85 cm for women), blood pressure≥130/80 mmHg, triglyceride≥150 mg/dL, fasting glucose≥110 mg/dL, and low high-density lipoprotein cholesterol (men<40 mg/dL, women<50 mg/dL). In that guideline, subjects who have more than 3 abnormal values mentioned above were defined as metabolic syndrome subjects. "
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    ABSTRACT: We investigated how serum low-density lipoprotein (LDL) level is related to various isoforms of apolipoprotein (ApoE) polymorphism in association with obesity and metabolic syndrome. We gathered total 332 sample of postmenopausal Korean women and analyzed ApoE isoforms, serum lipid level including LDL, blood pressure, fasting glucose, and anthropometry. The relationship between ApoE isoforms and serum lipid level, metabolic syndrome, and obesity was investigated. Six ApoE isoforms were found, ApoE2 [E2/2 (n=1), E2/3 (n=54), E2/4 (n=14)], ApoE3 (E3/3, n=200), ApoE4 [E3/4 (n=55), and E4/4 (n=8)]. The prevalence of metabolic syndrome and obesity showed higher ApoE3 isoform than that of other isoforms. In additon, ApoE3 isoform was related to higher serum LDL and total cholesterol level than to ApoE2 isoform. The odds ratio of having the highest LDL cholesterol quartile in ApoE3 with obesity, compared to ApoE2 without obesity, was 3.46 [95% confidence interval (CI); 1.07-11.14, p=0.037], and odds ratio of ApoE3 with metabolic syndrome compared to ApoE2 without metabolic syndrome was 5.06 (95% CI; 1.14-22.29, p=0.037). Serum LDL cholesterol was positively associated with obesity or metabolic syndrome in ApoE3 isoform. This study suggests that obesity or metabolic syndrome risk should be effectively managed in ApoE3 isomform groups to reduce serum LDL in postmenopausal Korean women.
    Full-text · Article · May 2011 · Yonsei medical journal
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    • "HDL-C is a highly heterogeneous lipoprotein that can be separated into two major subclasses (HDL-C2 and HDL-C3) and several minor subclasses based on density. Both major subclasses are inversely related to CHD risk,[11,15] and low HDL-C and low HDL particle concentration are associated with increased risk for CHD[16]. "
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    ABSTRACT: Some patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C) levels (and the cholesterol content of LDL subclasses), LDL particle number (approximated by apolipoprotein B), and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), and lipoprotein subclasses (Vertical Auto Profile II) and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels <150 mg/dL or ≥150 mg/dL. Both treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL1-4]) apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels <150 or ≥150 mg/dL. When assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels. (Registered at Clinical trial # NCT00276484).
    Full-text · Article · Mar 2010 · Lipids in Health and Disease
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