High-density lipoprotein subclasses in diabetes

This cross-sectional study evaluated high-density lipoprotein subclasses measured by a precipitation technique before and after treatment in men and women with types I and II diabetes. Total high-density lipoprotein cholesterol was lower in subjects of both sexes with untreated type I and type II diabetes, the change occurring primarily in subclass 2. Insulin therapy raised total and subclass 2 high-density lipoprotein levels in men and women with type I and type II diabetes, the predominant rise occurring in subclass 2. The improvement was unrelated to metabolic control. Normalization of total and subclass 2 high-density lipoprotein was not achieved in women with type II disease who had higher body weights and triglyceride levels. Treatment with oral hypoglycemic agents did not lower total high-density lipoprotein or subclass 2 levels. It is concluded that therapies affecting high-density lipoprotein produce the preponderant change in subclass 2, insulin therapy increases total and subclass 2 high-density lipoprotein but may not restore levels to normal in the presence of elevated body weight and lipid levels, there is no relation between control of diabetes and changes in total and subclass 2 high-density lipoprotein levels, and treatment with oral hypoglycemic agents does not adversely affect high-density lipoprotein levels.     

High-density lipoprotein cholesterol and longevity

Serum total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides were studied in three groups: (1) 85 healthy subjects aged 85-89 years, (2) 62 patients without coronary artery disease aged 38-62 years, and (3) 323 patients aged 32-69 years with triple-vessel disease diagnosed by coronary angiography. The mean values for total cholesterol were significantly higher in patients with triple-vessel disease than in those without coronary artery disease and in the elderly. Total cholesterol was over 6.5 mmol/l in 32% of the elderly, in 31% of patients without coronary artery disease and in 42% of patients with triple-vessel disease, but these differences were not significant. HDL-cholesterol and the ratio of HDL/total cholesterol were significantly higher in the elderly than in the patients without coronary artery disease and patients with triple-vessel disease. Serum HDL-cholesterol was over 1.0 mmol/l in 92% of the elderly, in 69% of patients without coronary artery disease and in 46% of patients with triple-vessel disease, the differences being significant between all groups.     

High-density lipoprotein cholesterol and carcinogenesis

High-density lipoprotein cholesterol (HDLC) has been recognized to be associated with atherosclerosis. In the past few years many studies have found that HDLC is also related to tumor development and progression. Despite some opposing views, a large number of studies support a negative association between HDLC and tumor incidence. Measuring serum HDLC concentrations may facilitate assessment of the prognosis of cancer patients and provide a biomarker for tumors. However, there is a lack of molecular mechanism studies on the link between HDLC and tumors. In this review we discuss the impact of HDLC on the incidence and prognosis of cancer in different systems, as well as prospects for the prediction and treatment of cancer in the future.     

High-density lipoprotein function recent advances

Although high-density lipoproteins (HDL) possess many features that contribute to the association between elevated HDL cholesterol and protection from atherosclerosis, these lipoproteins may be modified in certain individuals and/or circumstances to become proinflammatory. The ability of HDL to inhibit or paradoxically to enhance vascular inflammation, lipid oxidation, plaque growth, and thrombosis reflects changes in specific enzyme and protein components. The anti-inflammatory and proinflammatory functional properties of HDL can now be assessed using cell-based and cell-free assays. Acute or chronic systemic inflammation and the metabolic syndrome appear to render HDL proinflammatory. In contrast, statins and experimental agents such as apolipoprotein A-1 mimetics render HDL more anti-inflammatory. Functional characterization of HDL is a promising method for enhanced assessment of cardiovascular risk and effectiveness of risk reduction.     

High-density lipoprotein, low-density lipoprotein and coronary artery disease

Lipoprotein cholesterol data from the Framingham Heart Study show that low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels are important in determining risk for coronary artery disease (CAD). Increased LDL and decreased HDL cholesterol levels are associated with an increase in CAD. Such relations are independent of the usual coronary risk factors, such as cigarette use and hypertension. A 1% greater LDL value is associated with slightly more than a 2% increase in CAD over 6 years; a 1% lower HDL value is associated with a 3 to 4% increase in CAD. Even at total cholesterol levels less than 200 mg/dl, lower HDL levels are associated with increased myocardial infarction rates in both men and women. Death from CAD is increased when HDL levels are low, but there is no such relation between HDL level and cancer death. Triglyceride levels were associated with CAD in Framingham men and women, but the association was no longer significant in men after adjustment for HDL levels. The major determinants for greater HDL levels in Framingham participants included female sex, estrogen use, leanness, greater alcohol intake, exercise, abstinence from smoking and lack of diuretic or beta-blocker use.     

High-density lipoprotein function recent advances.

Although high-density lipoproteins (HDL) possess many features that contribute to the association between elevated HDL cholesterol and protection from atherosclerosis, these lipoproteins may be modified in certain individuals and/or circumstances to become proinflammatory. The ability of HDL to inhibit or paradoxically to enhance vascular inflammation, lipid oxidation, plaque growth, and thrombosis reflects changes in specific enzyme and protein components. The anti-inflammatory and proinflammatory functional properties of HDL can now be assessed using cell-based and cell-free assays. Acute or chronic systemic inflammation and the metabolic syndrome appear to render HDL proinflammatory. In contrast, statins and experimental agents such as apolipoprotein A-1 mimetics render HDL more anti-inflammatory. Functional characterization of HDL is a promising method for enhanced assessment of cardiovascular risk and effectiveness of risk reduction.     

High-density lipoprotein and glycosylated hemoglobin in nondiabetic individuals

We investigated associations of high-density-lipoprotein (HDL) cholesterol, apolipoprotein A-I, and triglyceride levels with hemoglobin A1 (HbA1) and insulin levels in nondiabetic subjects (137 women and 111 men). In women, HDL cholesterol, apolipoprotein A-I, and log-triglyceride values were significantly correlated with those of HbA1 and log-fasting insulin. These univariate associations persisted when age and Quetelet's index were included as covariates in multiple regression analyses. Conversely, univariate associations of HDL cholesterol and log-triglyceride levels with Quetelet's index were diminished by the addition of insulin values to multivariate models. Insulin levels and Quetelet's index were highly correlated. Although there were weaker associations in men, apolipoprotein A-I and HbA1 values were inversely related. These data suggest that HDL cholesterol and apolipoprotein A-I levels are closely linked to glucose metabolism in nondiabetic individuals.     

High-density lipoprotein/apolipoprotein A-I infusion therapy

Strategies to decrease the progression and burden of atherosclerosis by capitalizing on the protective effect of high-density lipoprotein (HDL) and/or apolipoprotein A1 (apoA-I) levels remain active. Although efforts to raise HDL through the administration of oral agents are still being pursued, the disappointing results demonstrated with torcetrapib, an agent that elevated serum HDL and apoA-I levels through the inhibition of cholesterol ester transfer protein, have raised questions regarding this approach. An alternate strategy that consists of short-term infusions of reconstituted HDL or apoA-I is currently under evaluation. Several infusion compounds have been evaluated in clinical trials that utilize cardiovascular imaging technologies and biomarkers to assess potential clinical efficacy. Although these compounds are still in early-stage development, the results of these trials have supported the viability of this line of investigation. This review addresses the potential of HDL and/or apoA-I infusions as a possible therapeutic strategy for the treatment of coronary artery disease.     

High-density lipoprotein: Antioxidant and anti-inflammatory properties

The ability of high-density lipoprotein (HDL) to promote cholesterol efflux is an important component of its ability to protect against cardiovascular disease. In addition, the anti-inflammatory properties of HDL are important as well. As part of the innate immune system, HDL appears to have evolved to increase inflammation in the presence of an acute phase response but to inhibit inflammation in the absence of an acute phase response. In a study of humans with coronary heart disease, it was found that the patients who had proinflammatory HDL prior to statin therapy (and half of them despite a profound decrease in plasma lipids following statin therapy) continued to have proinflammatory HDL. Anti-inflammatory HDL was effective in promoting cholesterol efflux whereas proinflammatory HDL was relatively weak in its ability to promote cholesterol efflux. Oxidative alterations of the main protein of HDL, apolipoprotein A-I, impaired its capacity to promote cholesterol efflux from monocyte macrophages. Therefore, HDL composition, structure, and function appear to be more crucial than HDL cholesterol concentrations in determining risk for cardiovascular disorders.     

High-density lipoprotein cholesterol and coronary heart disease

There is a large body of evidence demonstrating an inverse correlation between circulating levels of high-density lipoprotein (HDL) cholesterol and cardiovascular disease risk. For every 1-mg/dL increase in HDL, it is estimated that the risk of cardiovascular events decreases by 2% to 3%. HDL is one of many factors that contribute to the regulation of the atherosclerotic process. HDL mediates reverse cholesterol transport and exhibits numerous beneficial properties, including antioxidant, antiinflammatory, and antithrombotic effects on the vasculature. Recent studies have expanded our understanding of the vasoprotective mechanisms of HDL to include enhanced nitric oxide production and improved endothelium-dependent relaxation. Progress has also been made in determining the molecular mechanisms that mediate reverse cholesterol transport. Recently published National Cholesterol Education Program Adult Treatment Panel guidelines have broadened the definition of low levels of HDL and encourage more aggressive screening and treatment of lipid abnormalities. Several therapeutic interventions can augment HDL concentrations, and there is increasing evidence that these interventions improve cardiovascular outcomes. Research focusing on defining the molecular roles of HDL will likely identify potential therapeutic targets for decreasing the incidence and progression of coronary heart disease. This review highlights the role of HDL in coronary heart disease, from basic mechanisms of action to recent clinical trial results.     

High-density lipoprotein cholesterol is reduced in patients with sarcoidosis

PURPOSE: Sarcoidosis is a disease in which the proliferation of monocyte-macrophage-derived cells is observed. In other diseases characterized by expansion of the monocyte-macrophage system, such as Gaucher's disease and myeloid metaplasia, abnormalities of lipoprotein metabolism have been demonstrated. To determine whether similar abnormalities in lipoprotein cholesterol concentrations could be identified in patients with sarcoidosis, we studied total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol as well as triglyceride levels in 52 patients with biopsy-proven sarcoidosis. PATIENTS AND METHODS: Patients had no other medical disorders and were not being treated with corticosteroids or antimalarial agents. Blood samples were collected by venipuncture after an overnight fast. Plasma total cholesterol and triglyceride levels were measured using enzymatic techniques. Lipoprotein cholesterol was quantified by lipoprotein fractionation. HDL cholesterol was measured as cholesterol remaining in the supernatant after precipitation of LDL and very-low-density lipoprotein from whole plasma by the heparin-maganese chloride method. Computation was used to determine the level of LDL cholesterol. RESULTS: We found significantly reduced levels of total cholesterol (183.9 +/- 27.6 versus 194.3 +/- 16.5 mg/dl, mean +/- SD, p = 0.021) and HDL cholesterol (41.2 +/- 13.0 versus 51.9 +/- 6.1 mg/dl, p = 0.0001) in sarcoid patients versus an age-, sex-, and race-matched reference group. Differences were not observed in triglyceride or LDL cholesterol levels (p greater than 0.05). CONCLUSION: These findings are similar to those observed in the myeloproliferative diseases, Gaucher's disease, and rheumatoid arthritis and suggest a functional role for monocytes-macrophages in the regulation of serum lipoprotein cholesterol levels.