Small dense LDL

After assessment and control of LDL cholesterol, patients with serum triglycerides of 200 to 499 mg/dL (2.26 to 5.64 mmol/L) should be assessed for atherogenic dyslipidemia (low HDL cholesterol and increased small-dense LDL particles) and metabolic syndrome. 

Niacin (vitamin B3) has broad applications in the treatment of lipid disorders when used at higher doses than those used as a nutritional supplement. Niacin inhibits fatty acid release from adipose tissue and inhibits fatty acid and triglyceride production in liver cells. This results in an increased intracellular degradation of apolipoprotein B, and in turn, a reduction in the number of VLDL particles secreted (Fig. 9-4). The lower VLDL levels and the lower triglyceride content in these particles leads to an overall reduction in LDL cholesterol as well as a decrease in the number of small, dense LDL particles. Niacin also reduces the uptake of HDL-apolipoprotein A1 particles and increases uptake of cholesterol esters by the liver, thus improving the efficiency of reverse cholesterol transport between HDL particles and vascular tissue (Fig. 9-4). Niacin is indicated for patients with elevated triglycerides, low HDL cholesterol, and elevated LDL cholesterol.3... 

Diabetic dyslipidemia is characterized by hypertriglyceridemia, low HDL, and minimally elevated LDL. Small, dense LDL (pattern B) in diabetes is more atherogenic than larger, more buoyant forms of LDL (pattern A). 

Hypertriglyceridemia is associated with increased risk of coronary disease. VLDL and IDL have been found in atherosclerotic plaques. These patients tend to have cholesterol-rich VLDL of small-particle diameter and small, dense LDL. Hypertriglyceridemic patients with coronary disease or risk equivalents should be treated aggressively. Patients with triglycerides above 700 mg/dL should be treated to prevent acute pancreatitis because the LPL clearance mechanism is saturated at about this level. 

Badiou S, De Boever CM, Dupuy AM, Baillat V, Cristol JP, Reynes J. Small dense LDL and atherogenic lipid profile in HIV-positive adults influence of lopinavir/rito-navir-containing regimen. AIDS 2003 17 772-4. 

Saturated fatty acids 19 g/1 Increase HDL, small dense LDL, and total cholesterol. Inhibition of bacteria, virus... 

Low-fat, high-carbohydrate diets have been shown to lower plasma low-density lipoprotein (LDL) cholesterol levels. At the same time, these diets decrease anti-atherogenic high-density lipoprotein (HDL)-cholesterol, and increase concentrations of plasma triglycerides, lipoprotein[a] (Lp[a]), and small dense LDL, plus increasing insulin resistance. Overall, these changes are likely to increase the risk of coronary heart disease (Willett, 2002 Kris-Etherton et al., 2002 Sanders, 2003). 

Later epidemiological studies demonstrated that the low-density lipoprotein (LDL)-cholesterol, which is the predominant cholesterol carrier, like total cholesterol, was positively associated with the risk of CHD. On the other hand, HDL-cholesterol was negatively associated with the risk of CHD. Even between individuals having the same LDL-cholesterol level, those with a predominance of small, dense LDL particles have a much higher risk of CHD than individuals with a predominance of large, buoyant LDL particles (Gurr et al., 2002). It is notable that the Ci2 o, Ci4 o and Ci6 o fatty acids that increase total and LDL-cholesterol the most, concomitantly increase the levels of anti-atherogenic HDL-cholesterol, such that there can be a beneficial decrease in the total HDL ratio (Mensink et al., 2003). 

LDL-cholesterol levels is accompanied by an increase in small, dense LDL particles, triglycerides and insulin and a decrease in HDL-cholesterol level (Krauss, 2001), all of which are risk factors for CHD. 

In the early 1990s, a series of well-designed clinical studies convincingly demonstrated that TFAs increased plasma total and LDL-cholesterol to levels similar to those produced by saturated fatty acids. More than this, TFAs reduced plasma HDL-cholesterol level. The overall effect was that the ratio of LDL-cholesterol to HDL-cholesterol was approximately double that for an equivalent intake of saturated fatty acids (Ascherio et al., 1999). In addition, TFAs adversely affect other CHD risk factors. Plasma triglycerides and Lp[a] levels are increased (Ascherio et al., 1999) and it was shown recently that consumption of TFAs was associated with a deleterious increase in small, dense LDL particles (Mauger et al., 2003). 

Doctors now recognize that small, dense particles of LDL cholesterol are more dangerous than larger, buoyant particles. Niacin causes a shift from small, dense LDL to large, buoyant particles. No prescription drug can do that ... 

Familial combined hyperlipidemia is characterized by elevations in total cholesterol and triglycerides, decreased HDL, increased apolipoprotein B, and small, dense LDL. It is associated with premature CHD and may be difficult to diagnose because the lipid levels do not consistently display the same pattern. 

Lipoprotein(a), homocysteine, serum amyloid A, and small, dense LDL (pattern B). 

AGls have no significant effect on total and LDL-cholesterol [38]. However, recently published investigations in patients with IGT analyzing LDL-subfractions reveal a decrease in small dense LDL [39]. No significant effects have been shown on HDL-cholesterol in the STOP-NIDDM study... 

Keywords dyslipidaemia, LDL-cholesterol, small dense LDL, HDL-cholesterol, statins, fibrates, ezetimibe, nicotinic acid. 

When LDL particles are small and dense, there will be an increased particle number for a given LDL-cholesterol concentration. As there is one molecule of apo B per LDL particle, measurement of plasma apo B helps to identify the presence of small, dense LDL as the level will be higher than expected for the LDL-cholesterol concentration [25],... 

Tan KC, Cooper MB, Ling KL, et al. Fasting and postprandial determinants for the occurrence of small dense LDL species in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia the involvement of insulin, insulin precursor species and insulin resistance. Atherosclerosis. 1995 113 273-287. 

R 727 M. Mishima, Direct Measurement of Hydrogen Bonds with Multidimensional NMR , Seibutsu Kagaku Kaishi, 2003,81,142 R 728 K. Miyamoto, Structures of Peptides Related to the Inactivation Gate on Sodium Channels , Yakugaku Zasshi, 2002,122,1123 R 729 H. Mokuno, Small, Dense LDL and Oxidative Stress , Kekkan Igaku, 2003,4, 538... 

VLDL is metabolized via intermediate density lipoprotein (IDL) to LDL in the plasma by the action of lipoprotein lipase [72], Hepatic lipase may also contribute to the formation of TG-rich LDL particles [73], The increased production/decreased clearance of VLDL also may result in the increased production of precursors of small dense LDL (sd-LDL) particles [57,74,75], Such sd-LDL particles have been shown to contribnte to vascnlar diseases, as LDL receptors have a reduced affinity for sd-LDL, and sd-LDL are more vulnerable to oxidative modification [76-78], Numerous clinical stndies have shown increased CVD in subjects with high prevalence of sd-LDL [79], In animal models and in human diabetic conditions, sd-LDL levels are elevated [80,81] and snch accumulation appears to be accompanied by decreased paraoxonase 1 (PONl) activity. PONs are antioxidant enzymes that are known to detoxify H2O2 and lipid peroxides [82,83], The presence of PONl in lipoproteins also protects the... 

Hirayama, S., and Miida, T. Small dense LDL An emerging risk factor for cardiovascular disease. 2012 414 215-24. 

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