A Guide to Dyslipidemia

What is dyslipidemia? Dyslipidemia is defined as an abnormal plasma lipid status. Common lipid abnormalities include elevated levels of total cholesterol (TC), low-density lipoprotein (LDL), Lipoprotein a (Lp(a)) and triglycerides (TGs); low levels of high-density lipoprotein (HDL) and a preponderance of small dense LDL particles. These abnormalities can be found alone or in combination. Dyslipidemia & atherosclerosis essentials By Christie M. Ballantyne, James H. O'Keefe, Antonio M. Gotto Dyslipidemia is one of the top 5 major risk factors leading to cardiovascular disease. Its treatment has been shown to improve prognosis. Morbidity and mortality is substantially reduced in successfully treated as compared to non-treated dyslipidemic controls. Elisabeth Steinhagen-Thiessen te al. Dyslipidemia in primary care prevalence, recognition, treatment and control: data from the German Metabolic and Cardiovascular Risk Project (GEMCAS). Cardiovascular Diabetology 2008, 7:31 Assessing coronary heart disease risk A number of well-characterized factors like advanced age, hypertension, dyslipidemia, diabetes and smoking, contribute to cardiovascular risk. Integration of these factors using the Framingham calculation estimates the absolute 10-year risk for coronary heart disease (CHD), which can be used to guide therapy. Recent studies have demonstrated that additional markers, including elevated lipoprotein(a), homocysteine, sitosterol and particularly C-reactive protein (CRP), are also associated with increased risk for CHD. Assessment of global risk is particularly important in lipid management, as the LDL-C target goals are determined by risk category. Wilson PW. Assessing coronary heart disease risk with traditional and novel risk factors. Clin Cardiol. 2004 Jun;27(6 Suppl 3):III7-11. Diagnosis, Lipid evaluation and lipid goals A fasting lipid profile (TC, TGs, HDL and calculated LDL) should be obtained in all adults 20 yr and should be repeated every 5 yr. Lipid measurement should be accompanied by assessment of other cardiovascular risk factors like diabetes mellitus, cigarette use, hypertension, family history etc. Although there are differences in defining dyslipidemia and the goals to achieve when treating dyslipidemia there is a general trend to recommend low treatment targets for total cholesterol (TC) and LDL-cholesterol (LDL-C) in all major guidelines (Table 1). Elisabeth Steinhagen-Thiessen te al. Dyslipidemia in primary care prevalence, recognition, treatment and control: data from the German Metabolic and Cardiovascular Risk Project (GEMCAS). Cardiovascular Diabetology 2008, 7:31

Table 1. Treatment targets for total cholesterol (TC) and LDL-cholesterol (LDL-C) in the ESC and NCEP guidelines The European guideline on cardiovascular disease prevention in clinical practice for example recommends a TC of below 190 mg/dl (5.0 mmol/l) and an LDL-C of below 115 mg/dl (3.0 mmol/l) for the general population. When additional comorbidity is present (coronary artery disease (CAD), other cardiovascular disease (CVD) or diabetes mellitus) the goals are even lower: < 175 mg/dl (4.5 mmol/l) for TC and < 100 mg/dl (2.6 mmol/l) for LDL-C. De Backer G, et al. European guidelines on cardiovascular disease prevention in clinical practice: third joint task force of European and other societies on cardiovascular disease prevention in clinical practice. Eur J Cardiovasc Prev Rehabil 2003 , 10(4):S1-S10. The National Cholesterol Education Program (NCEP) guidelines chose another approach to define LDL-C targets based on the presence of additional risk factors: For patients with maximum 1 risk factor LDL-C levels of < 160 mg/dl (4.1 mmol/l) are targeted. Patients with 2 or more risk factors or a 10-year risk for CAD (myocardial infarction or CAD death) of less than 20% LDL-C levels < 130 mg/dl (3.4 mmol/l) are targeted. If patients already show CAD or CAD risk equivalent (other clinical forms of atherosclerotic disease, diabetes mellitus, or a 10 year-risk for CAD greater than 20%) an LDL-C goal of < 100 mg/dl (2.6 mmol/l) is recommended which is identical to the European guideline. Executive Summary of 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 III). J Am Med Ass 2001 , 285(19):2486-2497. Treatment options Available treatments include life-style interventions and pharmacotherapy and these treatments have been shown to successfully alleviate the extent of dyslipidemia if applied rigorously. Elisabeth Steinhagen-Thiessen te al. Dyslipidemia in primary care prevalence, recognition, treatment and control: data from the German Metabolic and Cardiovascular Risk Project (GEMCAS). Cardiovascular Diabetology 2008, 7:31 Five classes of drugs are available for the treatment of dyslipidemia, each with different effects on the various lipid and lipoprotein parameters (Table 2): 1. Statins are the most potent drugs available for reducing LDL-C. They bring about moderately lower triglyceride levels and modestly increase HDL-C levels. 2. Bile acid sequestrants mainly affect LDL-C. They have minimal effects on HDL-C and little or no effect on triglyceride concentrations. These drugs are a good option for patients who are intolerant of statins. 3. Niacin (vitamin B3) increases HDL-C levels but moderately lowers LDL-C and triglyceride levels and increases LDL particle size. 4. Fibrates exert their greatest effects on triglyceride levels, have moderate effects on HDL-C and mild effects on LDL-C and increase LDL particle size. Even using intensive statin monotherapy, many patients fail to achieve all the desired lipid goals and remain at high residual risk of cardiovascular events.

5. Cholesterol absorption inhibitors lower LDL-C concentrations and have a modest effect on HDL-C and triglycerides. Robert L. Talbert. Current Recommendations for the Treatment of Dyslipidemia. P&T, February 2004, Vol. 29 No. 2, 104-112 When statins fail Even using intensive statin monotherapy, many patients fail to achieve all the desired lipid goals and remain at high residual risk of cardiovascular events (Fig 1 and 2). In view of the still unproven decisively intensive "statin as monotherapy" strategy and "residual risk" concept, it is logical to ask whether other strategies, particularly fibrate/statin combination therapy, could be more beneficial and safer. Alexander Tenenbaum and Enrique Z Fisman. "If it ain't broke, don't fix it": a commentary on the positive-negative results of the ACCORD Lipid study. Cardiovascular Diabetology 2010, 9:24 Keith Ferdinand and David S. Kountz. New Approaches to Managing Dyslipidemia: Risk Reduction Beyond LDL-C. http://cme.medscape.com/viewprogram/15713 Combination therapy Mixed dyslipidemia, characterized by high LDL-C, low HDL-C, high triglycerides and high non-LDL lipids is frequently seen in high-risk patients with cardiometabolic risk factors such as diabetes, metabolic syndrome and obesity. In this setting, over and above the LDL-C levels, monitoring and management of HDL-C and other non-LDL components is critical to manage patient risk, as these other lipid parameters have been shown to be strong independent predictors of clinical events. Furthermore, studies have shown that aggressive intervention to treat mixed lipid profile can improve patient outcomes. In this regard, emerging data have the potential to improve evidence-based care for treating mixed dyslipidemia. Advances In Combination Therapy for Mixed Dyslipidemia, http://cme.medscape.com/sites/advances/mixed-dyslipidemia Given the therapeutic profile of the Given the therapeutic profile of the fibrates, combination with a statin fibrates, combination with a statin provides a suitable treatment strategy in individuals at high coronary risk, provides a suitable treatment with undesirable levels of triglycerides and LDL-C and low HDL-C. Such an strategy in individuals at high approach suggests advantages in terms of low dose and complementary mechanism of action. The accumulating clinical evidence supports the use of coronary risk. this combination therapy. In clinical trials, treatment with fenofibrate and a statin resulted in significantly greater lipid-modifying benefit than either agent as monotherapy, with reduction in LDL-C by 31-46% and triglyceride levels by 32-50% and elevation of HDL-C by 19-34%, in a variety of patient groups including those with overt type 2 diabetes. M. John Chapman. Fibrates: Therapeutic Review: Combination with a Statin. British Journal of Diabetes and Vascular Disease. 2006;6(1):11-18,20. Conclusion Dyslipidemia is one of the top 5 major risk factors leading to cardiovascular disease. Although statins are the mainstay of the treatment, intensive statin monotherapy fails to achieve all the desired lipid goals and patients remain at high residual risk of cardiovascular events. Given the therapeutic profile of the fibrates, combination with a statin provides a suitable treatment strategy in individuals at high coronary risk, with undesirable levels of triglycerides and LDL-C and low HDL-C. This approach has advantages in terms of low dose and complementary mechanism of action.