The Metabolic SyndromeImportance and Management of Dyslipidemia in the Metabolic Syndrome
Section snippets
Clinical Features of the Metabolic Syndrome
The prevalence of the metabolic syndrome, particularly in the United States, is alarmingly high. Furthermore, trends predict that as the rates of obesity and diabetes increase, worldwide prevalence will continue to rise. Metabolic syndrome as defined by ATP III was examined by the Third National Health and Nutrition Examination Survey (NHANES III) in 8814 adults.6 In the United States, the prevalence of metabolic syndrome in adults over the age of 20 was nearly a quarter of the population
Association of Diabetes Mellitus and Cardiovascular Disease Risk
It is recognized that many of the individual criteria for the metabolic syndrome place a person at a higher risk for developing both diabetes and CVD, especially CHD. Thus, aggressive screening and treatment, particularly of dyslipidemia, is of vital importance for those at high risk. The San Antonio Heart Study evaluated 1734 nondiabetics with the metabolic syndrome and evaluated impaired glucose tolerance (IGT)/insulin levels as an independent predictor of type 2 diabetes at an 8-year
Significance of Dyslipidemia in the Metabolic Syndrome
As stated previously, two of the components of the ATP III classification of the metabolic syndrome are elevated triglycerides and decreased levels of HDL cholesterol. Considerable data from epidemiologic, lipid intervention, and serial coronary angiographic trials indicate that HDL is the lipid particle that correlates best with overall CHD. Although there is an inverse relationship between triglycerides and HDL, and high triglycerides are associated with many other factors related to coronary
Therapeutic Strategies
The goals for managing the metabolic syndrome are aimed at preventing predictable complications, including type 2 diabetes and CVD events.28 The clinical management of dyslipidemia in the metabolic syndrome involves both therapeutic lifestyle changes and pharmacotherapy.
Nonpharmacologic Therapy
Therapeutic lifestyle changes include dietary restriction of calories, simple carbohydrates, and saturated fat and increased intake of soluble fiber, monounsaturated fats, and omega-3 fatty acids or fish oils. In addition, a mainstay of therapy is increasing regular aerobic exercise and intense efforts at achieving and maintaining an ideal body weight.4
In the Diabetes Prevention Program of 3234 patients with IGT, one group received placebo, another group received metformin titrated to 850 mg
Drug Therapy
Although the atherogenic dyslipidemia in the metabolic syndrome mainly involves elevated triglycerides and low HDL, initial pharmacologic therapy is aimed at lowering LDL levels (Table 2).4 After LDL cholesterol goals are achieved, secondary goals include non-HDL cholesterol levels (total cholesterol - HDL), and the goal for non-HDL levels in patients with elevated triglycerides and/or low HDL are generally 30 mg/dL higher than for LDL (i.e., if the LDL goal is less than 100 mg/dL, the non-HDL
Statins
The statin family inhibits the rate-determining step in cholesterol biosynthesis and is effective in the metabolic syndrome by reducing all ApoB containing lipoproteins, as well as hs-CRP. In the 4S study, patients post myocardial infarction with only high LDL had a 21% placebo event rate and had a 14% event reduction with simvastatin. On the other hand, the placebo event rate was 36% and 51%, respectively, in patients with the metabolic syndrome and diabetes and these groups had a greater than
Drug Combinations
Substantial data indicate the efficacy and safety of statin therapy to improve plasma lipids and reduce major CVD events in multiple groups of patients, including those with metabolic syndrome and/or diabetes. As reviewed elsewhere, plant stanols, plant sterols, and soluble fiber can all be added to statin therapy to aid in further lowering of LDL cholesterol.48 However, more potent therapies are also available to treat dyslipidemia, either as monotherapy or, more commonly, combined with
Fibrates
The two fibrates currently used clinically are gemfibrozil and fenofibrate. These agents mitigate atherogenic dyslipidemia and appear to reduce the risk of CVD in patients with metabolic syndrome.13 These agents are the drugs of choice for markedly elevated triglycerides, lowering triglycerides at times by more than 50% (25-30% reduction in patients with low levels of triglycerides) and generally increasing levels of HDL by 10% (but increases of over 25% can occur in patients with
Niacin
Nicotinic acid, or niacin, is perhaps the most underutilized agent to treat patients with dyslipidemia.48., 53., 54. It produces significant improvements in almost all aspects of the lipid profile, including lowering total cholesterol and LDL by 15%, reducing triglyceride by 25% to 30%, and reducing hs-CRP by 15% to 25% and is the best drug to increase HDL (generally by 25-30% but by more than 40% in patients with low HDL and hypertriglyceridemia). In addition, it is also the best drug to
Ezetimibe
Therapy with ezetimibe reduces intestinal cholesterol absorption by 54%, and 10 mg daily doses have produced 15% to 20% reductions in LDL cholesterol when used as monotherapy, and 20% to 25% additional LDL cholesterol reductions when added to statin therapy. In addition, ezetimibe slightly raises HDL and reduces the level of triglycerides by approximately 10%. Ezetimibe can be safely added to statin therapy without significant drug interactions. Besides adding to a statin's effects to lower LDL
Omega-3 Fatty Acids (Fish Oil)
Because of substantial effects on reperfusion arrhythmias, improving autonomic function, and reducing the risk of sudden cardiac death, we routinely recommend fish oils for our patients with known atherosclerosis or those with high-risk (e.g., patients with the metabolic syndrome and/or diabetes).66 However, for this purpose, we recommend doses of eicosapentaenoic acid and docosahexaenoic acid of 800 to 1000 mg/day, doses that may prevent sudden cardiac death but that do not lower triglycerides.
Conclusion
Substantial data support the critical role that atherogenic dyslipidemia plays in the metabolic syndrome and overall CVD risk. These risks can be substantially reduced by lipid intervention using therapeutic lifestyle changes and vigorous pharmacologic therapy, including statins alone or combined with other potent pharmacologic therapies, as discussed in this review.
References (66)
- et al.
Prevalance and profile of metabolic syndrome in patients following acute coronary events and effects of therapeutic lifestyle changes with cardiac rehabilitation
Am J Cardiol
(2003) - et al.
The metabolic syndrome
Lancet
(2005) - et al.
Apolipoprotein A-I containing lipoproteins in coronary artery disease
Atherosclerosis
(1987) - et al.
on behalf of the CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicenter randomized placebo-controlled trial
Lancet
(2004) - et al.
Effects of rosuvastatin, atorvastatin, simvastatin and pravastatin on atherogenic dyslipidemia in patients with characteristics of the Metabolic Syndrome
Am J Cardiol
(2005) Alternative approaches to lipid-lowering therapy
Am J Cardiol
(2002)- et al.
Marked benefit with sustained-release niacin therapy in patients with "isolated" very low levels of high-density lipoprotein cholesterol and coronary artery disease
Am J Cardiol
(1992) - et al.
Fifteen-year mortality in coronary drug project patients: long-term benefit with niacin
J Am Coll Cardiol
(1986) - et al.
Niacin in patients with diabetes mellitus and coronary artery disease
Am J Cardiol
(2001) - et al.
Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project)
Am J Cardiol
(2005)
Effect of coadministration of ezetimibe and simvastatin on high-sensitivity C-reactive protein
Am J Cardiol
Autonomic function, omega-3, and cardiovascular risk
Chest
Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition
Circulation
Cardiovascular risk associated with the metabolic syndrome
Curr Diab Rep
Associations between different anthropometric measurements of fatness and metabolic risk parameters in non-obese, healthy, middle-aged men
Int J Obes Relat Metab Disord
Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, Executive And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III)
JAMA
Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation
Diabet Med
Increasing prevalence of the metabolic syndrome among U.S. Adults
Diabetes Care
Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study
Diabetes Care
Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study
Circulation
The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men
JAMA
Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults
Circulation
Third National Health and Nutrition Examination Survey (NHANES III); National Cholesterol Education Program (NCEP). NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older
Diabetes
Adiposopathy: sick fat causes high blood sugar, high blood pressure and dyslipidemia
Future Cardiology
Alterations in lipoprotein lipase in insulin resistance
Int J Obes Relat Metab Disord.
Triglycerides are major determinants of cholesterol esterification/ transfer and HDL remodeling in human plasma
Arterioscler Thromb Vasc Biol
Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes?
JAMA
Cholesterol efflux, cholesterol esterification, and cholesteryl ester transfer by LpA-I and LpA-I/A-II in native plasma
Arterioscler Thromb Vasc Biol
Precipitation of 125I-labeled lipoproteins with specific polypeptide antisera: Evidence for two populations with differing polypeptide compositions in human high density lipoproteins
Biochemistry
Associations of HDL 2 and HDL 3 subtractions with ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study
Arterioscler Thromb Vasc Biol
A prospective, population-based study of low density lipoprotein particle size as a risk factor for
Can J Cardiol
A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction
JAMA
Atherogenic lipoprotein phenotype: a proposed genetic marker for coronary heart disease risk
Circulation
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