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 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 and the role of statins.

Low levels of high-density lipoprotein cholesterol (HDL-C) are currently considered to be a major risk factor for the development of coronary artery disease (CAD). Deficiencies in the HDL metabolic pathway promote atherosclerosis and contribute to CAD. Low HDL-C levels are included in the Framingham 10-year risk assessment for CAD although they are not yet targeted for therapy. Recent clinical trials have shown benefits from raising HDL-C, particularly in patients with lower baseline levels. The statin class of drugs, used primarily to lower the level of low-density lipoprotein-cholesterol, may be able to raise the HDL-C level as well. Statins could potentially affect HDL-C by different modes of action, most importantly by altering reverse cholesterol transport. Among the currently available statins, simvastatin has demonstrated the most consistent ability to raise HDL-C level, but further large-scale studies at an early stage will be needed to prove the antiatherogenic effects of this class of drugs.     

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.     

High-density lipoprotein cholesterol levels as a marker of reverse cholesterol transport

Dramatic advances have been made over the last decade in understanding the role of low-density lipoprotein (LDL) in atherosclerotic cardiovascular diseases and how to manage elevated levels of LDL cholesterol. Understanding the role of high-density lipoprotein (HDL) and how to intervene therapeutically in HDL action offers the possibility of even greater benefits. Epidemiologic studies have shown a strong inverse relation between HDL cholesterol and the risk of coronary artery disease (CAD). Whereas several subfractions of HDL can be identified, none convincingly offers better predictive value than total HDL cholesterol. Apolipoprotein A-I, the major apolipoprotein of HDL, also is inversely related to atherosclerotic risk. Unfortunately, measurements of HDL cholesterol or apolipoprotein A-I are considerably less precise and less accurate than measurements of total or LDL cholesterol. The biologic phenomena responsible for these epidemiologic relations are not yet clear. Moreover, several apparently contradictory observations and puzzling exceptions to the simplistic inverse relation of HDL cholesterol to CAD suggested by epidemiologic studies have created considerable confusion. The current confusion is not likely to be resolved until HDL metabolism and the cellular and molecular events responsible for the apparent protective effects of HDL are better understood. One current hypothesis that could explain the protective effects of HDL is that it mediates reverse cholesterol transport, the process by which cholesterol is removed from sites of deposition and delivered to the liver for excretion. From the standpoint of current therapy, each intervention that changes HDL cholesterol levels must be evaluated individually, on its own merit, in light of its effect on atherosclerosis and coronary events rather than on alterations in HDL cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-density lipoprotein cholesterol and apolipoprotein A-I levels at diagnosis in patients with non-insulin dependent diabetes

Summary High-density lipoprotein (HDL) cholesterol levels were decreased in patients with non-insulin dependent diabetes at diagnosis when matched with a control population for sex, age, obesity, alcohol consumption and cigarette smoking. There was no association between serum HDL-cholesterol concentration and the percentage of glycosylated haemoglobin A₁ (HbA₁). Serum HDL-cholesterol levels were lower in diabetics over the whole range of serum triglyceride levels, and particularly in hypertriglyceridaemic diabetics. Serum apolipoprotein A-I levels were not decreased in diabetics with normal serum triglyceride levels, so that the ratio of HDL cholesterol to apolipoprotein A-I was significantly decreased in diabetics (p<0.005). Decreased HDL cholesterol levels in non-insulin dependent diabetes could be relevant to the subsequent development of atherosclerosis.     

High-density lipoprotein cholesterol therapies: the next frontier in lipid management

Current cholesterol treatment guidelines target low-density lipoprotein cholesterol as the primary goal of therapy and recommend statins as first line therapy. However, despite aggressive treatment and success at reaching the recommended goals, coronary heart disease is still a leading cause of morbidity and mortality. Thus, other lipoproteins, such as high-density lipoprotein, are now being looked to as the next promising targets of therapy to help reduce the burden of coronary heart disease and atherosclerosis. This review details currently available strategies to raise high-density lipoprotein cholesterol, and then turns to several new compounds in development that target the varying components of the complex metabolism of high-density lipoprotein.     

High-density lipoprotein cholesterol and left ventricular hypertrophy in essential hypertension.

OBJECTIVE: The proportion of left ventricular (LV) mass variability explained by blood pressure in essential hypertension is small, and several non-haemodynamic determinants of LV mass have been identified or hypothesized. This study examines the possible relation between blood lipids and LV mass in hypertension. DESIGN: Never-treated non-diabetic hypertensive patients. SETTING: Hospital hypertension outpatient clinics in Umbria, Italy. PATIENTS: We investigated the association between high-density lipoprotein (HDL)-cholesterol and echocardiographic LV mass in 1306 never-treated subjects with essential hypertension. Subjects with previous cardiovascular events, diabetes and current or previous antihypertensive or lipid-lowering therapy were excluded. RESULTS: HDL-cholesterol showed an inverse association with LV mass (r = -0.30, P < 0.001). No association was found between LV mass and total or low-density lipoprotein cholesterol. With multiple linear regression analysis we tested the independent contribution of several potential determinants of LV mass in women and in men. Average 24 h blood pressure (both pulse and mean), body mass index, height, stroke volume, age (all P < 0.01) and low HDL-cholesterol (P < 0.0001 in women, P < 0.001 in men) were associated with a greater LV mass in both sexes. Triglycerides showed a weak univariate association with LV mass in women (r = 0.11, P < 0.02), which did not hold in a multivariate analysis. CONCLUSIONS: Low HDL-cholesterol is an independent predictor of LV mass in untreated hypertensive subjects. Common hormonal and metabolic mechanisms, including insulin resistance, could explain this association, which may contribute to the adverse prognostic significance of low HDL-cholesterol levels.     

High-density lipoprotein cholesterol and angiographic coronary artery disease in black patients

The clinical epidemiology of coronary artery disease (CAD) among black patients has not been well described, particularly in relation to the impact of the major risk factors. Lipoprotein profiles and other risk factors were measured in 114 black patients undergoing cardiac catheterization for probable CAD. Patients (coronary narrowing of 50% or greater; n = 63) were compared to those without significant stenoses (n = 51). Total cholesterol and low-density lipoprotein cholesterol (LDLC) were both significantly associated with the presence of CAD in men and women; however, high-density lipoprotein cholesterol (HDLC) had discriminatory value only for women. The ratio of total cholesterol to HDLC (TC:HDL) separated patients from control subjects in both sexes, most efficiently among women, and was the only lipid variable associated with CAD in the age group over 55 years. Hypertension and angina were frequent in both groups and did not identify those with disease. In summary, LDLC was the best predictor among the lipids for men (likelihood ratio = 9.4) and TC:HDL was the best indicator of disease among women (likelihood ratio = 15.7). Low HDLC levels may, in part, account for the increased incidence of CAD among black women. Further population studies of factors leading to reduced HDLC, namely, obesity and diabetes, are needed.     

High-density lipoprotein cholesterol and the risk of nephropathy in type 2 diabetic patients

Background and aimsTo date, few studies have demonstrated the impact of variations in blood pressure, blood glucose and lipid levels on the progression of diabetic nephropathy (DN) in type 2 diabetic patients. This study aimed to assess the associations of mean values and variability in metabolic parameters with the development of DN in type 2 diabetic patients.Methods and resultsA total of 864 patients who had participated in a comprehensive diabetic care program for at least for 3 years were studied. Patients were stratified into progressor (n = 180) and non-progressor groups (n = 684) according to the status of progression of DN during the follow-up period. By Cox regression analysis, a higher mean HDL-C level was observed to be a protective factor against the progression of DN [hazard ratio (95% CI): 0.971(0.953–0.989), P = 0.002] and a higher HDL-C variation was found to be associated with a higher risk [hazard ratio (95% CI): 1.177(1.032–1.341), P = 0.015] of DN progression. By the Kaplan–Meier survival curve, patients with a higher HDL-C level and lower HDL-C variability were found to have the lowest risk of development of nephropathy.ConclusionsOur study demonstrated for the first time that type 2 diabetic patients under a standard disease management program who have a stable and a higher mean HDL-C level were associated with a lower risk of development of DN.     

High-density lipoprotein cholesterol and coronary artery disease: survey of the evidence

The epidemiologic evidence linking high-density lipoprotein (HDL) levels with coronary artery disease (CAD) is persuasive. Case-control studies have shown CAD patients to have lower HDL levels than control subjects. Several large-scale, observational epidemiologic studies in the United States and abroad have shown a strong independent inverse relation between HDL and CAD. Women have a lower incidence of CAD than men of the same age; this has been attributed to their higher HDL levels. Postmenopausal women taking estrogen replacement therapy have higher HDL and lower low-density lipoprotein (LDL) levels, and a much lower incidence of CAD. Statistical analysis suggests that much of this is attributable to HDL levels. In several clinical trials, reduced levels of total or LDL cholesterol have been accompanied by increased HDL levels. Cox proportional hazards analysis suggests that the increment in HDL levels made an independent contribution to the reduction in CAD risk. In several angiographic studies, the increase in HDL may have contributed to the decreased progression, increased stabilization and possible regression of coronary lesions. Despite this range of impressive evidence, a number of unresolved issues have prevented the emergence of a consensus regarding the prevention of CAD by increasing HDL levels. Between-population comparisons of HDL and CAD do not match the within-population relations. Animal research on the relation between HDL, atherogenesis and CAD has been relatively scanty. Although much evidence suggests that reverse cholesterol transport partially explains the protective effect of HDL, there are still doubts as to its role. Problems with measurement of HDL have inhibited widespread recommendations for its use in prevention programs.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-density lipoprotein cholesterol in male alcoholics with and without severe liver disease

In a study of 26 male alcoholics, the subgroup without severe liver disease showed significant elevation in high-density lipoprotein cholesterol (HDL) in the immediate post-intoxication period; HDL levels decreased to control levels after one to two weeks of abstinence. Those patients with advanced liver disease failed to show this ethanol-induced rise in HDL. We were not able to correlate these observations with any variation in sex hormone levels, nutritional indices, age or quantity of alcohol intake. We concluded that ethanol consumption in alcoholics is associated with an increase in HDL levels, which is offset by the development of alcoholic liver disease.     

High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies

The British Regional Heart Study (BRHS) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol (HDLC) and incidence of coronary heart disease was eliminated by covariance adjustment. Using the proportional hazards model and adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol, we analyzed this relation separately in the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF) and Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT). In CPPT and MRFIT (both randomized trials in middle-age high-risk men), only the control groups were analyzed. A 1-mg/dl (0.026 mM) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2% in men (FHS, CPPT, and MRFIT) and 3% in women (FHS). In LRCF, where only fatal outcomes were documented, a 1-mg/dl increment in HDLC was associated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality rates. The 95% confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably, and all contained the range 1.9-2.9%. HDLC levels were essentially unrelated to non-cardiovascular disease mortality. When differences in analytic methodology were eliminated, a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.     

High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trial.

AIMS: Patients with acute coronary syndrome (ACS) in the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study had diminished cardiovascular events after 16 weeks of treatment of atorvastatin 80 mg daily. We determined whether plasma lipoproteins at baseline and then at 6 weeks after randomization predicted clinical outcome. METHODS AND RESULTS: Cox proportional hazards models were constructed to determine relations between lipoproteins and clinical endpoint events. Baseline LDL cholesterol (LDL-C) did not predict outcome. In contrast, baseline HDL-C predicted outcome with a hazard ratio of 0.986 per mg/dL increment in HDL-C, P<0.001, indicating 1.4% reduction in risk for each 1 mg/dL increase in HDL-C. Atorvastatin treatment profoundly lowered LDL-C, but had minimal effect on HDL-C. Neither Week 6 LDL-C nor absolute change of LDL-C from baseline by Week 6 had any significant impact on clinical endpoints occurring between Week 6 and Week 16 after randomization. CONCLUSION: Plasma HDL-C, but not LDL-C, measured in the initial stage of ACS predicts the risk of recurrent cardiovascular events over the ensuing 16 weeks. LDL-C reduction does not account for the clinical risk reduction with atorvastatin treatment after ACS. This finding may suggest that the clinical benefit of atorvastatin after ACS is mediated by qualitative changes in the LDL particle and/or by non-lipid (pleiotropic) effects of the drug.     

High-density lipoprotein cholesterol levels of very old people in the diagnosis of dementia

Serum cholesterol fractions and triglycerides were determined in 68 female hospital patients over 90 years of age with senile dementia of Alzheimer type (AD; n = 22) with multi-infarct dementia (MID; n = 23) or without dementia (n = 23). There were no significant differences in serum HDL cholesterol levels between the three groups, but the ratio of high-density lipoprotein cholesterol (HDLC) to total cholesterol was lower in MID patients than in patients without dementia. In all three groups the concentrations of serum cholesterol, low-density lipoprotein cholesterol (LDLC) and triglycerides were relatively low and the concentration of HDLC was normal. The concentrations of serum triglycerides and very-low-density lipoprotein (VLDL) cholesterol were significantly (P less than 0.05) higher in MID patients than in AD patients. The mean levels of serum total cholesterol and LDLC were significantly (P less than 0.001) higher in MID patients than in patients without dementia. The mean levels of LDLC of AD patients were higher than in patients without dementia. The results do not support the suggestion that HDLC levels may be of diagnostic value in multi-infarct dementia.