Lipids Overview: Evaluating Cardiovascular Risk Factors and Treatment Options

 Speakers: Peter H. Jones, MD, Benjamin Ansell, MD, and Michael Bloch, MD

The introduction of statin therapies has helped healthcare professionals treat patients with cardiovascular disease. Still, challenges exist in managing these patients and evaluating the best way to determine if they are healthy or at risk of other health problems. 

Providers typically monitor low-density lipoprotein (LDL) cholesterol, but speakers at the 2013 Cardiometabolic Risk Summit indicated there is a need to evaluate non-high-density lipoprotein (non-HDL) cholesterol, apolipoprotein B, and other measures that also may be effective.


Peter H. Jones, MD, associate professor at Baylor College of Medicine in Houston, TX, said the guidelines from the National Cholesterol Education Program for LDL cholesterol and when to begin treatment are “too complicated.” The guidelines, released in 2002 and updated in 2004, have 5 categories of risk: lower, moderate, moderately high, high, and very high.1 They indicate that the drugs used should achieve at least a 30% to 40% reduction in LDL cholesterol. 

Since the guidelines were released nearly a decade ago, the treatment paradigm has changed and organizations have updated their recommendations. For instance, the American Heart Association indicated healthcare professionals should target an LDL cholesterol level <70 mg/dL for secondary prevention, while other organizations have revealed that the ideal HDL cholesterol is <40 mg/dL for men and <50 mg/dL for women.2-5

Alternative Predictors

For a long time, the prevailing opinion has been that lowering LDL cholesterol is the most important factor in reducing risk factors for cardiovascular disease, according to Jones. He cited a meta-analysis of 170,000 subjects from 26 randomized trials: 5 studies compared more versus less intensive statin regimens, while the remaining 21 evaluated statin therapy versus a control group.6 For all trials, lowering LDL cholesterol by at least 40 mg/dL led to a 22% risk reduction for any major cardiovascular event. The benefit was found regardless of a person’s baseline LDL cholesterol level.

“This is not a very appealing clinical practice, but that’s what the evidence says,” Jones said.

Instead of only considering LDL cholesterol, Jones suggested that apolipoprotein B and non-HDL cholesterol “are better predictors of what will happen to [people] in the future” when it comes to cardiovascular disease. Although LDL cholesterol is a good lipid biomarker, he said measuring apolipoprotein B and non-HDL cholesterol is more effective, particularly for patients with insulin resistance or those with high triglycerides. 

Non-HDL cholesterol is also an attractive option because it doesn’t cost any additional money, according to Jones. Healthcare professionals simply subtract HDL cholesterol from total cholesterol, and they can calculate a person’s non-HDL cholesterol.

Treatment Goals

The American Diabetes Association and the American College of Cardiology have identified treatment goals for patients, too.7 They defined the highest risk patients as those with known cardiovascular disease or diabetes plus at least 1 other major cardiovascular disease risk factor such as smoking, hypertension, and family history of premature coronary artery disease. 

For the highest risk patients, the goals are:

• <70 mg/dL for LDL cholesterol.

• <100 mg/dL for non-HDL cholesterol.

• <80 mg/dL for apolipoprotein B.

They defined high risk patients as those without diabetes or known cardiovascular disease but at least 2 other major cardiovascular disease risk factors or those with diabetes but no other major cardiovascular risk factors. 

For the high risk patients, the goals are: 

• <100 mg/dL for LDL cholesterol.

• <130 mg/dL for non-HDL cholesterol.

• <90 mg/dL for apolipoprotein B.


Benjamin Ansell, MD, professor of medicine at the University of California, Los Angeles, said most therapies primarily target LDL cholesterol and have a secondary target of non-HDL cholesterol. There is some debate on the correct target for drugs intended to deal with HDL cholesterol issues, whether they attempt to raise HDL cholesterol or target the composition or function of HDL—which is a complicated particle with a complicated mechanism of action. In fact, raising HDL cholesterol may not be necessary and may not help improve HDL-mediated cardiovascular risk.

Some of the proven methods used to decrease cardiovascular risk include lowering LDL cholesterol and triglycerides and adopting lifestyle measures—such as increased exercise, weight loss, improved diet, decreased alcohol consumption, and smoking cessation. 

Researchers in one study examined several interventions to modify HDL cholesterol by analyzing journal articles published from 1965 to May 2007, reviewing presentations at major clinical meetings from 2003 to 2007, and examining ongoing trials and treatment guidelines. After identifying 31 randomized controlled trials, they found that aerobic exercise and tobacco cessation increased HDL by 5% to 10%, decreased alcohol consumption increased HDL by 5% to 15%, and dietary factors increased HDL by up to 5%.8

Several trials have examined the use of drugs on cardiovascular outcomes with mixed results. Ansell recommended that patients receive statin-based therapies and improve their lifestyle modifications through more exercise and a better diet. 

“The focus should be on reducing and impacting cardiovascular risk,” he said.


Michael Bloch, MD, medical director of vascular medicine and anticoagulation services at the Renown Institute for Heart and Vascular Health in Reno, NV, said that even patients taking statins have residual cardiovascular risk. He cited a study that examined lipid levels in the first 24 hours after 136,905 patients were admitted to 541 hospitals for coronary artery disease between 2000 and 2006.9 

The authors found that the mean LDL cholesterol was 104.9 mg/dL, the mean HDL was 39.7 mg/dL, and the mean triglycerides were 161 mg/dL. In addition, only 17.6% of patients had LDL cholesterol <70 mg/dL and 54.6% had HDL cholesterol <40 mg/dL. Of the patients who did not have a history of coronary artery disease, 72.1% had LDL cholesterol <130 mg/dL and 41.5% had LDL cholesterol <100 mg/dL. 

In the PROVE-IT [Pravastatin or Atorvastatin Evaluation and Infection Therapy] trial,10 22.4% of patients who received 80 mg of atorvastatin daily died or had a major cardiovascular event compared with 26.3% of patients who took 40 mg of pravastatin daily (p=.005). The trial included 4162 patients with acute coronary syndrome. The median LDL cholesterol was 62 mg/dL in the atorvastatin group and 95 mg/dL in the pravastatin group.

Although statins are effective, Bloch said they only target LDL cholesterol. However, there are other components of cardiometabolic risk, including insulin resistance, lifestyle issue such as smoking and an unhealthy diet, and poor glycemic control and hypertension control.

To measure residual risk, Bloch suggested healthcare professionals should examine HDL cholesterol, non-HDL cholesterol, apolipoprotein B, particle numbers and sizes, perform imaging studies, and evaluate risk scores. 

The Reynolds Risk Score is a tool to predict if a person will have a heart attack, stroke, or major heart disease in the next 10 years. It asks for a person’s age and information about smoking, systolic blood pressure, high sensitivity C-reactive protein, total cholesterol, HDL cholesterol, and
parental history of myocardial infarction before they turn 60 years of age. 


The CADILLAC [Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications] risk score evaluates patients with acute myocardial infarction and percutaneous coronary intervention. Questions include if a patient is >65 years of age, has a Killip classification 2 or 3, has a baseline ejection fraction <40%, has anemia, has renal insufficiency, or has 3-vessel disease. A decrease in ejection fraction is the best predictor of cardiovascular risk, according to Bloch.


Bloch said risk scores are “pragmatic,” but they are sometimes “cumbersome” to calculate, so doctors do not use them often enough. Although measuring residual risk is possible, successfully treating it “is a much more difficult and profound question.” He added that trials of drugs, such as nicotinic acid that increase HDL cholesterol, are not encouraging.

Finally, Bloch also discussed subgroup analyses of 4 studies that suggested adding fibrates to statin therapies could help in patients with diabetes, low HDL cholesterol, and high triglycerides.11 Other options to reduce residual risk include omega-3 polyunsaturated fat supplements (ie, eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], and alpha-linolenic acid). 

The American Heart Association recommends 1 gm per day of EPA or DHA acid after patients suffer from myocardial infarction.12 Patients with hypertriglyceridemia require much higher doses, and results are mixed when it comes to using omega-3 products to reducing cardiovascular events in those patients.

For patients at high risk of cardiovascular disease, Bloch recommends beginning treatment with statins. Healthcare professionals should monitor them closely and evaluate their LDL cholesterol as well as their non-HDL cholesterol, apolipoprotein B, or LDL particles. He said relying solely on LDL cholesterol is not sufficient. If patients do not achieve their goals when treated with statins, they should add another medication (drug and dosage dependent on each individual).  ■


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