Physician's Weekly Article - Managing Lipoproteins in Patients With Cardiometabolic Risk

       A consensus statement on lipoprotein management in patients with cardiometabolic risk sheds light on the importance of treating lipoprotein abnormalities in an effort to improve outcomes in these individuals.

      According to published research, risk factors for diabetes and cardiovascular disease (CVD) often cluster, including obesity, insulin resistance, high glucose levels, abnormal concentrations of lipoproteins in the blood, and high blood pressure. Each of these factors increases the risk of CVD, and the clustering of these conditions is referred to as cardiometabolic risk (CMR). “Historically, physicians have paid most of their attention to hyperglycemia as the primary cause for complications in diabetes, but clinicians are increasingly focusing on diabetes as a cardiovascular disease,” explains Peter Sheehan, MD. “In fact, we’ve learned that cardiovascular risk is conferred even before the onset of hyperglycemia in pre-diabetes. One of the features of pre-diabetes and diabetes is the presence of CMR characteristics.”

      In the April 2008 issue of Diabetes Care and April 15, 2008 Journal of the American College of Cardiology, the American Diabetes Association (ADA) and American College of Cardiology (ACC) co-published a consensus statement on lipoprotein management in patients with CMR. The statement indicates that lipoprotein abnormalities—including elevated triglyceride levels, low HDL cholesterol levels, and increased numbers of small dense LDL particles—are commonly present in patients with CMR. Specific lipid treatment goals have been established for patients with type 2 diabetes or CVD, but guidelines for treatment of lipoprotein abnormalities in high-risk patients without diabetes or CVD have been less intense and may have underestimated lifetime CVD risk.

      Considering Residual CVD Risk

      Clinical trials have demonstrated that directing therapies—most notably statins—at LDL cholesterol lowering can reduce the risk of CVD events in patients with diabetes and those without it but with other CVD risk factors. However, Dr. Sheehan says that even with adequate LDL cholesterol lowering, many patients on statins have significant residual CVD risks. “The goal of the ADA/ACC consensus statement was to identify lipoprotein parameters other than LDL or non-HDL cholesterol that can provide additional prognostic information, yield more information about the effectiveness of therapy for lipoprotein abnormalities, and indicate more appropriate treatment targets. Many patients with CMR or diabetes have normal levels of LDL cholesterol, but also have increased numbers of small dense LDL particles and other atherogenic lipoproteins.”

      The ADA/ACC consensus statement identifies several lipoproteins and lipoprotein components that appear to be most clinically relevant to CMR. Elevated LDL cholesterol and LDL particle numbers have been well established as major predictors of CVD, including patients with CMR or diabetes, but Dr. Sheehan says other lipoproteins are also important. “Most doctors understand the LDL cholesterol is an important measure for cardiovascular risk, but measuring, assessing, and monitoring non-HDL cholesterol [total cholesterol minus HDL cholesterol] and apolipoprotein B [apoB], which measures the total burden of particles that are considered most atherogenic, are also helpful to gaining a better understanding of CMR.”

      Treatment Goals & Recommendations

      Several treatment goals have been recommended in the ADA/ACC consensus statement, based on evaluation of available evidence (Table 1). “Patients with CVD and those with diabetes and one or more other CVD risk factors are at the highest risk of experiencing a cardiac event,” Dr. Sheehan says. “These patients should be treated to specific LDL, non-HDL, and apoB goals in order to optimize outcomes. Patients with neither diabetes nor known clinical CVD but two or more additional major CVD risk factors and those with diabetes but no other major CVD risk factors are considered high-risk patients and have slightly different lipoprotein targets. Physicians should keep these targets in mind and strive to reach these goals to reduce CMR.”

      The ADA/ACC consensus statement indicates that statins should be used for most patients with CMR who have an abnormal distribution of lipoproteins in their blood (Table 2), but Dr. Sheehan notes that it is important for clinicians to assess lipoprotein parameters besides LDL. “Statins have been shown to lower CVD event rates by 25% to 50% depending on the endpoint, but there’s still a high absolute risk to consider. We can’t just focus on LDL because non-HDL and apoB levels are also significant in patients with CMR. Measuring these lipoproteins is not more costly and can help clinicians ascertain a more accurate measure of risk.”

      Dr. Sheehan emphasizes that 57 million Americans are considered to have pre-diabetes. “Because type 2 diabetes is a largely preventable disease, the potential impact of interventions is significant. Efforts that address lipoprotein abnormalities can have a profound impact on CMR. To be successful, we need to find patients with CMR early and initiate therapy quickly and aggressively. The hope is that the ADA/ACC consensus statement, in addition to efforts like the ADA’s Cardiometabolic Risk Initiative, will further encourage physicians to focus on the prevention, recognition, and treatment of all risk factors for type 2 diabetes and CVD.”

      Peter Sheehan, MD has indicated to Physician’s Weekly that he has received research grants from Tissue Repair Company, PamLab, Genzyme, and Sanofi-Aventis. He is also a director at Greystone Pharmaceuticals, and is on the Scientific Advisory Board of Advanced BioHealing. He has served as a consultant for Hypermed and Calrete and is on the speaker’s bureau for EV3, Bristol-Myers Squibb/Sanofi, Merck, and Organogenesis.