Usefulness of HDL Cholesterol as a Target to Lower Risk of CHD
Multiple lines of evidence show that high-density lipoproteins (HDL) protect against coronary heart disease (CHD), and that low blood levels of HDL cholesterol (HDLc) indicate high risk of a coronary event. Major epidemiological studies show that a low HDLc is a strong predictor of CHD, and this relationship occurs at any level of low-density lipoprotein cholesterol (LDLc) or triglycerides, demonstrating independence. When the HDLc level is raised by drug therapy, coronary atherosclerosis is decreased and CHD events are lessened. Increases in HDLc are in fact independently correlated with coronary angiographic and clinical benefit. HDL stimulates the removal of cholesterol from cells in the vascular wall. The cholesterol is taken up by HDL and shuttled in part to the liver for excretion in the bile.
Experiments in transgenic mice provide proof that increased HDL secretion protects against atherosclerosis caused by an atherogenic diet or genetic hyperlipidaemia. In humans, HDL has direct beneficial effects on coronary arterial vasodilation. This compelling scientific evidence thus justifies HDLc as a target to reduce risk of CHD. An international group of experts in epidemiology, clinical and basic science formed a consensus that an HDLc concentration of 1.0 mmol/L (40 mg/dL) is a realistic clinical guideline for patients at high risk of a coronary event. Specific diet and drug therapies were recommended.
Low high-density lipoprotein cholesterol (HDLc) often occurs in the presence of other risk factors. Lack of exercise and over- consumption of high-carbohydrate foods depress HDLc. When energy expenditure does not keep up with rampant intake, so encouraged by intense competition among food companies to commandeer consumers' digestive systems, obesity is the consequence. Obesity is expanding rapidly in incidence, and Britain has one of the steepest trajectories worldwide. Diabetes and insulin resistance in adulthood can be nearly entirely attributed to such adipogenic tendencies, humans being genetically programmed to store fat as much as possible.
Obesity, insulin resistance and diabetes cause other serious metabolic problems, especially high triglyceride levels, and elevated concentrations of highly atherogenic triglyceride-rich lipoprotein remnants (chylomicrons and very low-density lipoprotein [VLDL]) indicated, (imperfectly) by high triglyceride levels. These linked metabolic disorders are called 'the metabolic syndrome'.
There is debate among experts about whether obesity or insulin resistance is the proximal insult that ignites this metabolic conflagration. Obesity and insulin resistance are not perfectly correlated, and it is well known to clinicians that some fortunate obese people have normal glucose tolerance whereas some unfortunates who are just mildly overweight have insulin resistance. In either obesity or diabetes, metabolism of chylomicrons and VLDL is sluggish since the key enzyme effecting triglyceride hydrolysis, lipoprotein lipase, is low. This reduces HDL, since HDL itself is formed from components of chylomicron and VLDL metabolism as they circulate through the vasculature. This pathway, one of several that modulate HDL concentrations, links a high triglyceride with a low HDL concentration.
Although early mathematical attempts to unravel the relative importance of each element in this constellation may have been confounded by the biological interrelationships that bind them together, low HDLc turned out to confer independent risk, since its impact was not found to be secondary to these other associated conditions. In other words, depressed levels of HDLc herald increased risk for coronary heart disease (CHD) at all levels of low-density lipoprotein cholesterol (LDLc) and triglycerides, in people with diabetes and in non-diabetics, in men and women, and in the secondary as well as the primary prevention setting.
Abstract
Multiple lines of evidence show that high-density lipoproteins (HDL) protect against coronary heart disease (CHD), and that low blood levels of HDL cholesterol (HDLc) indicate high risk of a coronary event. Major epidemiological studies show that a low HDLc is a strong predictor of CHD, and this relationship occurs at any level of low-density lipoprotein cholesterol (LDLc) or triglycerides, demonstrating independence. When the HDLc level is raised by drug therapy, coronary atherosclerosis is decreased and CHD events are lessened. Increases in HDLc are in fact independently correlated with coronary angiographic and clinical benefit. HDL stimulates the removal of cholesterol from cells in the vascular wall. The cholesterol is taken up by HDL and shuttled in part to the liver for excretion in the bile.
Experiments in transgenic mice provide proof that increased HDL secretion protects against atherosclerosis caused by an atherogenic diet or genetic hyperlipidaemia. In humans, HDL has direct beneficial effects on coronary arterial vasodilation. This compelling scientific evidence thus justifies HDLc as a target to reduce risk of CHD. An international group of experts in epidemiology, clinical and basic science formed a consensus that an HDLc concentration of 1.0 mmol/L (40 mg/dL) is a realistic clinical guideline for patients at high risk of a coronary event. Specific diet and drug therapies were recommended.
Introduction
Low high-density lipoprotein cholesterol (HDLc) often occurs in the presence of other risk factors. Lack of exercise and over- consumption of high-carbohydrate foods depress HDLc. When energy expenditure does not keep up with rampant intake, so encouraged by intense competition among food companies to commandeer consumers' digestive systems, obesity is the consequence. Obesity is expanding rapidly in incidence, and Britain has one of the steepest trajectories worldwide. Diabetes and insulin resistance in adulthood can be nearly entirely attributed to such adipogenic tendencies, humans being genetically programmed to store fat as much as possible.
Obesity, insulin resistance and diabetes cause other serious metabolic problems, especially high triglyceride levels, and elevated concentrations of highly atherogenic triglyceride-rich lipoprotein remnants (chylomicrons and very low-density lipoprotein [VLDL]) indicated, (imperfectly) by high triglyceride levels. These linked metabolic disorders are called 'the metabolic syndrome'.
There is debate among experts about whether obesity or insulin resistance is the proximal insult that ignites this metabolic conflagration. Obesity and insulin resistance are not perfectly correlated, and it is well known to clinicians that some fortunate obese people have normal glucose tolerance whereas some unfortunates who are just mildly overweight have insulin resistance. In either obesity or diabetes, metabolism of chylomicrons and VLDL is sluggish since the key enzyme effecting triglyceride hydrolysis, lipoprotein lipase, is low. This reduces HDL, since HDL itself is formed from components of chylomicron and VLDL metabolism as they circulate through the vasculature. This pathway, one of several that modulate HDL concentrations, links a high triglyceride with a low HDL concentration.
Although early mathematical attempts to unravel the relative importance of each element in this constellation may have been confounded by the biological interrelationships that bind them together, low HDLc turned out to confer independent risk, since its impact was not found to be secondary to these other associated conditions. In other words, depressed levels of HDLc herald increased risk for coronary heart disease (CHD) at all levels of low-density lipoprotein cholesterol (LDLc) and triglycerides, in people with diabetes and in non-diabetics, in men and women, and in the secondary as well as the primary prevention setting.