When Low Cholesterol Isn't Enough: Assessing Options for Managing Residual Risk
Below are all the test questions with an explanation of the correct answer. Questions answered incorrectly will be highlighted.
- A recent analysis of lipid levels carried out in 136,905 patients hospitalized in the United States from 2000 to 2006 with coronary artery disease (CAD) identified which of the following? Answer: All of the above
- The goal of obtaining LDL-Cs of <100 mg/dL is being achieved in >1/2 of patients, but CAD is continuing to occur. Sachdeva et al. analyzed lipid levels obtained within the first 24 hours following hospital admission for CAD of 136,905 patients from 541 hospitals between 2000 and 2006. All patients had confirmed diagnoses of CAD. The patient data were extracted from the Get With the Guidelines database, a Web-based patient management tool used to collect clinical data, and was divided into LDL-C, HDL-C, and TG categories. More than half (56.4%) of the patients in this large cohort had admission LDL-C levels of <100 mg/dL, and only 21.1% were on lipid-lowering medications. In addition, 55% of the cohort had HDL-C levels of <40 mg/dL, and 35% had TGs >150 mg/dL.
- Which of the following describes residual cardiovascular (CV) risk? Answer: All of the above
- The concept of residual CV risk developed from results of the statin vs placebo-controlled trials that targeted secondary CV risk and were carried out in primary or high-risk patients. The statins provided major reductions in CV risk, but a significant risk remained. Thus, residual CVD risk is the risk that remains after patients have been treated with statins (including intensive statin therapy) to reduce LDL-C, or for those with LDL-C <70 mg/dL but have low HDL-C, diabetes, or other uncontrolled coronary heart disease (CHD) risk factors.
- Which of the following are indicators of CV risk despite attainment of LDL-C goals? Answer: All of the above
- A significant increase in risk exists if TGs are >150 mg/dL, even when adjusting for HDL levels. A strong positive and graded association exists between non–HDL-C and risk for CHD. Cholesterol is packaged into lipoproteins mainly in the form of cholesterol esters, and lipoproteins differ in size and cholesterol ester content. Small, dense LDL particles are relatively poor in cholesterol esters, but there are more small LDL particles required to give any specific value for the total cholesterol in the LDL fraction. The number of particles is a predictor of risk; therefore, the LDL-C measure can be misleading with regard to the risk contributed by these lipoproteins when small LDL is present. The LDL-C value measured in a standard lipid profile does not provide information about the size and atherogenicity of the LDL particle population.
- Which of the following are treatment targets recently identified by the American Diabetes Association (ADA) for patients with type 2 diabetes mellitus (T2DM)? Answer: LDL-C <100 mg/dL without CVD
- According to the 2010 ADA guidelines, statin therapy should be added to lifestyle therapy regardless of baseline lipid levels in diabetic patients. The lipid goal of <70 mg/dL is for patients with T2DM and CVD. New recommendations in 2010 include a LDL-C goal of <100 mg/dL in patients with diabetes, even if <40 years of age. Although desirable, raising HDL-C to >40 mg/dL in men, >50 mg/dL for women, and lowering TGs to <150 mg/dL are not targets.
- Which of the following lipid measurements or markers is useful in determining additional CV risk? Answer: All of the above
- LDL particle number and apoB are good surrogate measures for increased CV risk, and apoAI has an inverse relationship to the development of heart disease. Lipoprotein(a) is inherited and has a significant relationship with CV disease but requires a special test to determine levels. It would be important to obtain a lipoprotein(a) test in patients with a positive history of early CHD.
- Results from the randomized, placebo-controlled, double-blind Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial revealed which of the following? Answer: Risk was only reduced in T2DM patients with high TGs and low HDLs on a statin and fenofibrate.
- The ACCORD lipid trial was designed to determine if combination therapy with a statin plus a fibrate would reduce CV disease risk in patients with T2DM. Patients received simvastatin to achieve lipid guidelines and then were randomized in a double-blind design to placebo or fenofibrate. Mean baseline characteristics included an age of 62 years, total cholesterol 175 mg/dL, LDL-C 101 mg/dL, HDL-C 38 mg/dL, median TG of 162 mg/dL, and T2DM duration of 9 years. A benefit of fenofibrate therapy was only found in patients with elevated TGs and low HDLs. Therefore, ACCORD does not support the use of combination fenofibrate and simvastatin therapy compared with simvastatin monotherapy to decrease CVD events in T2DM patients with near-normal HDL-C and TG levels. Women who received fenofibrate appeared to have an increase in CVD events. This gender difference was not found in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial.
- Which of the following statements is true regarding HDL-C? Answer: All of the above
- Data from the Framingham study suggest that the risk of CHD relates to HDL-C levels, with CHD risk decreasing by half for each 20 mg/dL increase in HDL-C. The 4S trial examined the relationship between the risk of major coronary events (coronary death and nonfatal myocardial infarction) and baseline cholesterol levels in patients with CHD. Although risk was reduced by a statin in every quartile of baseline HDL-C, risk was higher among patients in the lower 2 quartiles compared with the higher 2 quartiles of HDL-C. Furthermore, a low HDL-C at baseline has been shown to be a key predictor of major CV events and death in ACS patients who had received a drug-eluting stent implantation. However, it remains unclear whether aggressively raising HDL-C will translate into improved clinical outcomes.
- Which of the following statements is true regarding current and possible future therapeutic options for dyslipidemia? Answer: All of the above
- In clinical trials, the CETP inhibitors have demonstrated an ability to significantly increase HDL-C. However, torcetrapib failed to affect the progression of CAD (% change in atheroma volume). Due to increased mortality, evaluation of torcetrapib has stopped, but other CETP inhibitors are under evaluation for safety in phase III trials. MTP inhibitors are a newer class of agents being evaluated for their ability to lower LDL-C. High interest exists for their possible use in patients with homozygous familial hypercholesterolemia. Niacin has been shown to be the most effective HDL-C-raising agent currently available. Laropiprant, a PGD2 receptor (DP1) antagonist, when administered in combination with extended-release niacin, decreases flushing.