Treating Diabetic Dyslipidemia: A Review of Practical Recommendations Based on Clinical Trials

Hospital Physician December 2006 27 Heart disease mortality in the United States has fallen substantially in the last several decades, primarily due to reductions in cardiovascular risk factors and improvements in heart disease treatments.1 Whether patients with diabetes mellitus (DM) have experienced a decline in heart disease mortality similar to that in the general US population has been a subject of debate. In relative terms, DM confers a twofold greater risk of cardiovascular disease (CVD)2 and mortality in the year following a myocardial infarction (MI), and in patients who survive to day 28 post-MI, the risk is approximately 2 times higher in men and 4 times higher in women with DM compared with their nondiabetic counterparts.3 The fact that the rates of type 2 DM, metabolic syndrome, and obesity continue to rise4,5 provides an additional impetus for more targeted and aggressive management of cardiovascular risk factors in patients with DM. In the majority of patients, the characteristic cardiovascular risk factors in type 2 DM include hyperglycemia, hypertension, modestly increased levels of low-density lipoprotein cholesterol (LDL-C), and decreased levels of high-density lipoprotein cholesterol (HDL-C).6 Decreased HDL-C along with elevated triglycerides and small, dense LDL-C particles are the characteristic features of diabetic dyslipidemia, which substantially increases the risk of CVD in patients with DM.7 Thus, intensive glycemic control alone is not likely to eliminate the excess risk of CVD in these patients.8 A multifactorial approach is warranted, as supported by results of the Steno-2 study.9 The high cardiovascular risk associated with DM warrants more aggressive lipid-lowering therapy, including reduction of LDL-C, in all patients with DM. Interestingly, LDL-C levels in patients with DM are typically not higher than LDL-C levels in matched controls and are often in the range that has been described as “borderline high” (ie, 130–159 mg/dL).7 However, other metabolic abnormalities also contribute to the increased CVD risk that accompanies DM. For example, aside from the absolute LDL-C level, the number of lowdensity lipoprotein particles is typically greater than suggested by the LDL-C level alone, as particles are smaller and denser in patients with DM than in the general population.7 It is also likely that synergistic interactions between modest elevations in LDL-C and other risk factors associated with the metabolic syndrome, which is common in persons with type 2 DM, enhance the pathophysiologic importance of LDL-C in this disease.7 Together these findings support LDL-C as a primary target of cardiovascular risk management in patients with DM. This article reviews practical recommendations for managing dyslipidemia in patients with DM based on results of many large epidemiologic and clinical trials. C l i n i c a l R e v i e w A r t i c l e