Treating Dyslipidemic Patients
Updated guidelines from the National Cholesterol Education Program give greater emphasis to lipoproteins other than low-density lipoprotein cholesterol (LDL) than previous guidelines. Although statins remain first-line therapy for most patients to lower LDL, combination therapy is the next logical step in achieving goals in patients with mixed dyslipidemia or elevated LDL despite statin therapy. As the prevalence of diabetes, metabolic syndrome, and atherogenic dyslipidemia rises, the importance of treating the total lipid profile becomes even more crucial. Niacin, fibrates, and bile acid sequestrants are effective in combination with statins in lowering LDL, triglycerides, and total cholesterol levels and increasing high-density lipoprotein cholesterol (HDL). Although combination therapies may increase the risk of myopathy, both fibrate-statin and niacin-statin combinations are considered safe. In addition, niacin-statin therapy reduces atherosclerotic progression and coronary events. New pharmacologic formulations exist that will further affect treatment: a single-tablet combination of lovastatin and extended-release niacin is available, as is ezetimibe, a cholesterol-absorption inhibitor. In all, both HDL and triglyceride levels correlate with cardiovascular risk and should be considered secondary targets of therapy. Combination therapy can be safe and effective and can be constructed to affect all lipoprotein parameters.
Ischemic cerebrovascular and cardiovascular events are leading causes of morbidity and mortality in the United States. Although knowledge of their pathophysiology has grown dramatically over the past 30 years, leading to effective treatment strategies and reductions in mortality, these events still are leading causes of death. A major causal factor in development of ischemic diseases is high cholesterol. According to data from the Framingham Heart Study, persons with total cholesterol levels above 260 mg/dl had a 33% risk of death versus 15% in persons with levels below 180 mg/dl over a period of 30 years (Figure 1). Disorders of lipoprotein metabolism, including lipoprotein overproduction and deficiency, are classified as dyslipidemias. They may manifest as one or more of the following: elevated total cholesterol, low-density lipoprotein cholesterol (LDL), and triglyceride levels, and a decreased high-density lipoprotein cholesterol (HDL) level.
(Enlarge Image)
Data from the Framingham Heart Study show the percentages of patients still alive over time based on initial cholesterol levels. Note that after 30 years, whereas 85% of patients with baseline cholesterol levels below 180 mg/dl (solid line) were still alive, approximately one third of those with baseline cholesterol levels above 260 mg/dl (dotted line) had died. Adapted with permission from reference 3.
Despite increased public and professional awareness and numerous treatment options, dyslipidemia remains an increasingly important modifiable risk factor for coronary heart disease (CHD). An estimated 102 million American adults have total blood cholesterol levels of 200 mg/dl and above, and 41.3 million have levels of 240 mg/dl or greater. The high-fat Western diet, a growing obesity problem, and increasingly common conditions such as metabolic syndrome are adding to the growing population of persons with lipid abnormalities. The metabolic syndrome is a constellation of metabolic risk factors such as abdominal obesity, elevated blood pressure, insulin resistance, and atherogenic dyslipidemia. Atherogenic dyslipidemia is common in patients with metabolic syndrome, diabetes, and premature CHD and is characterized by small, dense LDL particles, elevated triglycerides, and low HDL, also known as the atherogenic triad. The character of atherogenic dyslipidemia makes for more efficient endothelial penetration and elevated oxidizability, and is responsible for the high risk associated with this atherogenic triad.
The third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults -- Adult Treatment Panel (ATP) III reaffirms that LDL is the primary target of cholesterol-lowering therapy. Although ATP III refers to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), bile acid sequestrants (BAS), and niacin as the primary means to achieve desired LDL goals, both primary and secondary prevention trials and a clean safety profile support statins as the first choice in this effort. Beyond the primary goal of LDL reduction, other lipid risk factors must be considered, including triglyceride and HDL levels. Although statins are the first line of treatment, they do not always improve the entire lipid profile to desired levels. In addition, emergence of metabolic syndrome and other genetic lipid abnormalities force consideration of other intensive lipid-modifying strategies and possible combination therapy to meet NCEP goals. Combination therapy is an important option for patients who have the atherogenic triad or are not meeting lipid goals with monotherapy.
Updated guidelines from the National Cholesterol Education Program give greater emphasis to lipoproteins other than low-density lipoprotein cholesterol (LDL) than previous guidelines. Although statins remain first-line therapy for most patients to lower LDL, combination therapy is the next logical step in achieving goals in patients with mixed dyslipidemia or elevated LDL despite statin therapy. As the prevalence of diabetes, metabolic syndrome, and atherogenic dyslipidemia rises, the importance of treating the total lipid profile becomes even more crucial. Niacin, fibrates, and bile acid sequestrants are effective in combination with statins in lowering LDL, triglycerides, and total cholesterol levels and increasing high-density lipoprotein cholesterol (HDL). Although combination therapies may increase the risk of myopathy, both fibrate-statin and niacin-statin combinations are considered safe. In addition, niacin-statin therapy reduces atherosclerotic progression and coronary events. New pharmacologic formulations exist that will further affect treatment: a single-tablet combination of lovastatin and extended-release niacin is available, as is ezetimibe, a cholesterol-absorption inhibitor. In all, both HDL and triglyceride levels correlate with cardiovascular risk and should be considered secondary targets of therapy. Combination therapy can be safe and effective and can be constructed to affect all lipoprotein parameters.
Ischemic cerebrovascular and cardiovascular events are leading causes of morbidity and mortality in the United States. Although knowledge of their pathophysiology has grown dramatically over the past 30 years, leading to effective treatment strategies and reductions in mortality, these events still are leading causes of death. A major causal factor in development of ischemic diseases is high cholesterol. According to data from the Framingham Heart Study, persons with total cholesterol levels above 260 mg/dl had a 33% risk of death versus 15% in persons with levels below 180 mg/dl over a period of 30 years (Figure 1). Disorders of lipoprotein metabolism, including lipoprotein overproduction and deficiency, are classified as dyslipidemias. They may manifest as one or more of the following: elevated total cholesterol, low-density lipoprotein cholesterol (LDL), and triglyceride levels, and a decreased high-density lipoprotein cholesterol (HDL) level.
(Enlarge Image)
Data from the Framingham Heart Study show the percentages of patients still alive over time based on initial cholesterol levels. Note that after 30 years, whereas 85% of patients with baseline cholesterol levels below 180 mg/dl (solid line) were still alive, approximately one third of those with baseline cholesterol levels above 260 mg/dl (dotted line) had died. Adapted with permission from reference 3.
Despite increased public and professional awareness and numerous treatment options, dyslipidemia remains an increasingly important modifiable risk factor for coronary heart disease (CHD). An estimated 102 million American adults have total blood cholesterol levels of 200 mg/dl and above, and 41.3 million have levels of 240 mg/dl or greater. The high-fat Western diet, a growing obesity problem, and increasingly common conditions such as metabolic syndrome are adding to the growing population of persons with lipid abnormalities. The metabolic syndrome is a constellation of metabolic risk factors such as abdominal obesity, elevated blood pressure, insulin resistance, and atherogenic dyslipidemia. Atherogenic dyslipidemia is common in patients with metabolic syndrome, diabetes, and premature CHD and is characterized by small, dense LDL particles, elevated triglycerides, and low HDL, also known as the atherogenic triad. The character of atherogenic dyslipidemia makes for more efficient endothelial penetration and elevated oxidizability, and is responsible for the high risk associated with this atherogenic triad.
The third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults -- Adult Treatment Panel (ATP) III reaffirms that LDL is the primary target of cholesterol-lowering therapy. Although ATP III refers to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), bile acid sequestrants (BAS), and niacin as the primary means to achieve desired LDL goals, both primary and secondary prevention trials and a clean safety profile support statins as the first choice in this effort. Beyond the primary goal of LDL reduction, other lipid risk factors must be considered, including triglyceride and HDL levels. Although statins are the first line of treatment, they do not always improve the entire lipid profile to desired levels. In addition, emergence of metabolic syndrome and other genetic lipid abnormalities force consideration of other intensive lipid-modifying strategies and possible combination therapy to meet NCEP goals. Combination therapy is an important option for patients who have the atherogenic triad or are not meeting lipid goals with monotherapy.
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