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Lipoprotein(a), homocysteine, and remnantlike particles: emerging risk factors
L J Seman1, J R McNamara, E J Schaefer
1Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Insights
Lipoprotein(a) [Lp(a)] is an independent risk factor for coronary heart disease (CHD). Measuring and treating elevated Lp(a), homocysteine, and remnantlike lipoprotein cholesterol can mitigate CHD risk.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Clinical Risk Factors
Background:
- Lipoprotein(a) [Lp(a)] has been recognized for over 35 years, with recent data confirming its role as an independent risk factor for coronary heart disease (CHD).
- In vitro studies indicate Lp(a) promotes atherogenesis through cholesterol uptake and fibrinolysis inhibition.
- Other independent CHD risk factors include homocysteine and remnantlike lipoprotein cholesterol.
Purpose of the Study:
- To review the role of Lp(a), homocysteine, and remnantlike lipoprotein cholesterol as independent risk factors for coronary heart disease (CHD).
- To discuss current therapeutic interventions for elevated levels of these risk factors.
Main Methods:
- Review of prospective and population-based prevalence data.
- Analysis of in vitro studies on Lp(a) mechanisms.
- Evaluation of diagnostic criteria and treatment guidelines.
Main Results:
- Elevated Lp(a) (cholesterol >10 mg/dL or mass >30 mg/dL) in patients with CHD or high risk warrants treatment with niacin or estrogen.
- Homocysteine levels >14 mumol/L should be managed with vitamin supplements (folate, B6, B12).
- Remnantlike lipoprotein cholesterol, associated with CHD risk in women, may be addressed by diet, fibric acid derivatives, or statins, though clear interventions are pending.
Conclusions:
- Lp(a), homocysteine, and remnantlike lipoprotein cholesterol are significant independent risk factors for CHD.
- Targeted treatments exist for Lp(a) and homocysteine.
- Further research is needed to establish definitive therapeutic strategies for remnantlike lipoprotein cholesterol.
Abstract:
Although lipoprotein(a) [Lp(a)] was first described more than 35 years ago, adequate prospective data have only recently supported Lp(a) as an independent risk factor for coronary heart disease (CHD). In vitro studies suggest that Lp(a) contributes to atherogenesis directly by cholesterol uptake and indirectly by the inhibition of fibrinolysis. In patients with CHD or a significant risk for CHD, Lp(a) should be measured and treated with either niacin or estrogen if the patient has Lp(a) cholesterol levels of more than 10 mg/dL or an Lp(a) mass of more than 30 mg/dL. In addition, homocysteine and remnantlike lipoprotein cholesterol are strongly supported by prospective or population-based prevalence data as independent risk factors for CHD. Homocysteine levels of more than 14 mumol/L should be treated with vitamin supplements of folate, B6, and B12. Remnantlike lipoprotein cholesterol is the product of a novel immunoassay that separates the partially hydrolyzed triglyceride-rich remnant particles. The association of these particles with CHD risk in women may explain the small independent CHD risk that triglycerides have in women in the Framingham Heart Study. A clear therapeutic intervention has not been documented but may include diet, fibric acid derivatives, or hydroxymethylglutamyl coenzyme A reductase inhibitors.