There are many peer-reviewed papers covering HDL-C and CVD, and it is frequently difficult for healthcare professionals to keep up with the literature. As a special service to our readers, CLI presents a few key literature abstracts from the clinical and scientific literature chosen by our editorial board as being particularly worthy of attention.
Usefulness of the TG/HDL-C ratio for predicting the mortality risk in type 2 diabetes: role of kidney dysfunction.
An increased level of the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) has been identified as an independent predictor for cardiovascular events in the general population and in some groups of high-risk patients, such as type 2 diabetes. The study described in this study evaluated whether a high TG/HDL-C ratio is associated with an increased risk of all-cause and cardiovascular mortality in type 2 diabetic subjects, and whether this risk is modified by the presence of kidney dysfunction. Three thousand and eighty-four type 2 diabetic outpatients were followed for a mean period of 4.9 years for the occurrence of mortality. The independent association between the TG/HDL-C ratio and all-cause and cardiovascular mortality was analysed by Cox proportional hazard models and adjusted for several potential confounders, including kidney function measures. During follow-up, 356 (12%) participants died, 46% from cardiovascular causes. A higher TG/HDL-C ratio (third vs. first tertile) was associated with an increased hazard ratio of all-cause mortality after adjustment for traditional risk factors, body mass index, hemoglobin A1c and medication use. After additional adjustment for renal function measures (estimated glomerular filtration rate or albuminuria), there was no association between the TG/HDL-C ratio and the risk of mortality. These findings suggest that the predictive role of a high TG/HDL-C ratio in type 2 diabetes on cardiovascular and all-cause mortality might be largely mediated by the presence of kidney dysfunction.
Zoppini G et al. Atherosclerosis. 2010 May 6.
Dysfunctional high-density lipoprotein and atherosclerosis.
High-density lipoprotein (HDL) is well established as a negative risk factor for the development of atherosclerosis. Epidemiologic, pathologic, and experimental studies have demonstrated a role for HDL in protection from coronary artery disease. HDL has been shown to reduce the risk from atherosclerosis by multiple pathophysiologic mechanisms. Low-density lipoprotein is a metabolic end product that can be recognised and cleared by specific hepatic receptors with excretion into the bile. However, low-density lipoprotein may also be scavenged in the periphery by the monocyte-macrophage system, with subsequent generation of lipid-laden foam cells. HDL may reduce the atherosclerotic burden by multiple potential mechanisms. HDL can interact with the foam cell to remove cholesterol via receptor-mediated binding, passive diffusion and alteration of intracellular cholesterol trafficking by ATP binding cassettes. The process of reverse cholesterol transport is a major mechanism by which HDL can remove cholesterol from the periphery, allowing it to be cleared by the liver and then excreted into the bile. However, HDL exhibits multiple additional potential beneficial physiologic effects. Endothelial function and repair is potentiated by HDL. Normal HDL has significant anti-inflammatory and antioxidant activity. Prostacyclin production and improvement in fibrinolytic balance is also attributed to normally functioning HDL, which is also intimately related to the metabolism of other circulating lipoproteins. However, multiple clinical studies have identified individuals with a significant atherosclerotic burden despite normal or elevated levels of HDL cholesterol. Clinical conditions associated with inflammation and oxidative stress have adversely altered the normal functions of HDL. Clinical assays have been developed to assess the functionality of HDL. Dysfunctional HDL may be returned to normal by diet, exercise, degree of fat intake, and pharmacologic approaches. Orally active mimetic proteins are in development and have shown clinical promise.
Ragbir S, Farmer JA. Curr Atheroscler Rep 2010 May 27.
LDL-C/HDL-C ratio predicts lipid-rich coronary plaque in patients with coronary artery disease.
This paper points out that the relationship between blood lipid profile and coronary plaque tissue characteristics and differences in the tissue characteristics between acute coronary syndrome (ACS) and chronic coronary artery disease (CCAD) are unclear. The purpose of the study presented in this paper was to compare the plaque tissue characteristics in patients with ACS and CCAD and to examine the relationship between the tissue characteristics and blood lipid profile. Integrated backscatter intravascular ultrasound (IVUS) and conventional IVUS were performed in patients with ACS (n=24) and CCAD (n=68) at the time of coronary intervention. Percent tissue volume and cross-section area of lipid pool, fibrous tissue, dense fibrous and calcification were defined in target lesions. The lipid pool area (LPA) in the ACS patients was significantly higher than in the CCAD patients. In the CCAD group, LPA/non-LPA ratio tended to be higher in the ACS than in the CCAD patients, and the LDL/HDL ratio was an independent predictor for LPA/non-LPA ratio. In addition, the LDL/HDL ratio was a useful index for the prediction of a high LPA/non-LPA ratio. An elevated LDL/HDL ratio may thus be a positive predictor for coronary lipid-rich plaque and plaque vulnerability in patients with CCAD.
Kimura T et al. Circ J. 2010 May 18.
Pharmacological intervention using reconstituted HDL changes in the lipid profile in spontaneously hypersensitive rats.
Reconstituted (r) high-density lipoprotein (HDL) protects against coronary artery disease by promoting reverse cholesterol transport (RCT), thereby preventing atherosclerosis. In addition, rHDL has many pleiotropic effects, such as anti-oxidant, anti-inflammatory and anti-thrombotic properties. In this study, the effects of chronic rHDL administration on blood pressure (BP), plasma lipoprotein, and charge-based HDL subfractions were examined. Thirteen male spontaneously hypertensive rats (SHRs) were randomly divided into two groups [control group (n = 6) and rHDL group (n = 7)] which received infusions of placebo [phosphate-buffered saline (PBS)] or rHDL (containing apolipoprotein A-I 6 mg/kg) administered intravenously every other day for three weeks. Systolic blood pressure (SBP) was measured regularly every four days from the beginning of the study. Three weeks after the beginning of the study, cardiac functions were recorded by echocardiography and plasma samples were collected. Although there were no significant differences in SBP, cardiac functions or biochemical parameters between the two groups, the level of intermediate-migrating HDL (iHDL) in the rHDL group was significantly lower than that in the control group based on an analysis by capillary isotachophoresis. Chronic administration of rHDL did decrease iHDL. Further studies are needed to understand the mechanisms by which rHDL affects lipid profiles and its relation to clinical outcomes.
Imaizumi S et al. Clin Exp Hypertens. 2010 May;32(3):202-8.
