Triglyceride-Rich Lipoproteins and High-Density Lipoprotein Cholesterol in Patients at High Risk of Cardiovascular Disease: Evidence and Guidance for Management

Perspective:

The following are 10 points to remember from the European Atherosclerosis Society Consensus Panel recommendations:

1. Optimal treatment including lifestyle intervention and pharmacotherapy aimed at lowering plasma concentrations of low-density lipoprotein cholesterol (LDL-C), reducing blood pressure, and preventing thrombotic events fails to ‘normalize’ risk in people at high risk of cardiovascular disease (CVD).

2. Post-hoc analyses of prospective trials in acute coronary syndrome and stable coronary heart disease reveal that elevated plasma levels of triglycerides and low plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are associated with a high risk, even at or below recommended LDL-C goals. And in diabetics, HDL-C is the second most important coronary risk factor, after LDL-C.

3. There is convincing evidence that elevated levels of triglyceride-rich lipoproteins (TRLs) and their remnants (chylomicron-R and VLDL-R) and low levels of HDL-C are cardiovascular risk factors that require therapeutic strategies for management. This is particularly true in persons with cardiometabolic risk associated with insulin resistance in whom post-prandial TRL remnants contribute to atherosclerotic plaque progression.

4. The functioning characteristic of circulating HDL particles in the healthy state includes reverse cholesterol transport, and anti-oxidative, anti-inflammatory, vasodilatory, and antithrombotic properties.

5. Lifestyle interventions influence the metabolism of HDL and TRL remnants as well as insulin resistance. Smoking increases TRL remnants and decreases HDL-C levels, which are reversed on quitting. Aerobic exercise causes long-lasting reduction in triglycerides by up to 20%, and increases in HDL-C by up to 10%. A diet high in fiber and foods with a low glycemic index can reduce recurrent coronary events in survivors of myocardial infarction. While a healthy lifestyle clearly is important in reducing CV risk, poor long-term adherence is a problem, and many require additional pharmacological intervention.

6. Evidence is supportive of therapeutic approaches aimed at concomitantly lowering TRL and raising HDL-C to reduce CV risk. Of these options, niacin, fibrates, and marine sources of omega-3 polyunsaturated fatty acids influence levels of multiple lipids and lipoproteins and, therefore, clinically beneficial effects observed cannot be ascribed solely to changes in any single lipoprotein fraction.

7. Niacin in combination with a statin has been shown to reduce progression of carotid and coronary disease even in patients without the atherogenic phenotype and despite a low LDL-C level. Its effects include up to a 30% increase in HDL-C, modest lowering of LDL-C and triglycerides, and several anti-atherosclerotic and antithrombotic properties.

8. Results from individual fibrate monotherapy outcomes trials in nondiabetics and a major trial in diabetes have been variable, and primarily indicate a reduction in nonfatal myocardial infarction and revascularization, but with no effect on stroke or CV death. Post-hoc analyses of several trials suggest a clinical benefit in the subgroup of patients with elevated triglycerides and low HDL-C, but no benefit was noted in diabetes without this lipid phenotype. A meta-analysis confirmed that fibrates on the background of statins provides clinical benefits in those with the atherogenic dyslipidemia, but not without. In type 2 diabetes mellitus, fibrate treatment reduces microvascular complications and retinopathy.

9. In summary, statins firmly remain the first-line treatment of choice for attainment of LDL-C goal in patients at high risk of CVD. After LDL-C goal attainment, however, and if triglyceride levels remain elevated (≥150 mg/dl) and HDL-C low (<40 mg/dl) despite intensive lifestyle intervention, the addition of fibrate or niacin may be considered.

10. The European Guidelines desirable lipid level in patients at high risk of CVD includes: LDL-C <100 mg/dl and <80 mg/dl in very high risk, triglycerides <150 mg/dl, HDL-C >40 mg/dl in men and >45 mg/dl in women, and non-HDL-C <100 mg/dl.

Clinical Topics: Acute Coronary Syndromes, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Diet, Exercise, Smoking

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Stroke, Life Style, Atherosclerosis, Plaque, Atherosclerotic, Exercise, Diabetes Mellitus, Type 2, Coronary Disease, Glycemic Index, Insulin Resistance, Smoking, Fibric Acids, Dyslipidemias, Cholesterol, HDL, Fatty Acids, Unsaturated, Niacin, Diet, Lipoproteins, HDL, Triglycerides, Diabetes Mellitus


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