Dr. Dayspring serves on the advisory board for LipoScience. Dr. Helmbold reports no financial relationships relevant to this article.
Add another item to your ever-growing list of responsibilities: monitoring your patients’ risk of atherosclerosis.
This task used to be the purview of internists and cardiologists but, because gynecologists are increasingly serving as a primary care provider, you need to learn to recognize and diagnose the many clinical expressions of atherosclerosis in your aging patients.
A crucial part of that knowledge is a thorough understanding of each and every lipid concentration parameter reported within the standard lipid profile. This article reviews those parameters, explains how to interpret them individually and in combination, and introduces a new paradigm: the analysis of lipoprotein particle concentrations as a more precise way to determine risk.
If used in its entirety, the lipid profile provides a significant amount of information about the presence or absence of pathologic lipoprotein concentrations. Far too many clinicians focus solely on low-density lipoprotein cholesterol (LDL-C) and ignore the rest of the profile. Failure to consider the other variables is one reason why atherosclerotic disease is underdiagnosed and undertreated in the United States in many patients—especially women.1
How to read a lipid panel in 6 quick steps
1. Look at the triglyceride (TG) level. If it is >500 mg/dL, treatment is indicated, and TG reduction takes precedence over all other lipid concentrations. If TG is <500 mg/dL, go to Step 2.
2. Look at the low-density lipoprotein cholesterol (LDL-C) level. If it is >190 mg/dL, drug therapy is indicated regardless of other findings. At lower levels, the need for therapy is based on the patient’s overall risk of cardiovascular disease (CVD). Therapeutic lifestyle recommendations are always indicated.
3. Look at high-density lipoprotein cholesterol (HDL-C). Increased risk is present if it is <50 mg/dL, the threshold for women. Do not assume that high HDL-C always means low CVD risk.
4. Calculate the total cholesterol (TC)/HDL-C ratio (a surrogate of apoB/apoA-I ratio). Increased risk is present if it is >4.0.
5. Calculate the non-HDL-C level (TC minus HDL-C). If it is >130 mg/dL (or >100 mg/dL in very-high-risk women), therapy is warranted. Newer data reveal that this calculation is always equal to, or better than, LDL-C at predicting CVD risk. Non-HDL-C is less valuable if TG is >500 mg/dL.
6. Calculate the TG/HDL-C ratio to estimate the size of LDL. If the ratio is >3.8, the likelihood of small LDL is 80%. (Small LDL usually has very high LDL-P.)
Why lipoproteins are important
There is only one absolute in atherosclerosis: Sterols—predominantly cholesterol—enter the artery wall, where they are oxidized, internalized by macrophages, and transformed into foam cells, the histologic hallmark of atherosclerosis. With the accumulation of foam cells, fatty streaks develop and, ultimately, so does complex plaque.
Lipids associated with cardiovascular disease (CVD) include:
- cholesterol
- noncholesterol sterols such as sitosterol, campesterol, and others of mostly plant or shellfish origin
- triacylglycerol, or triglycerides (TG)
- phospholipids.
Because lipids are insoluble in aqueous solutions such as plasma, they must be “trafficked” within protein-enwrapped particles called lipoproteins. The surface proteins that provide structure and solubility to lipoproteins are called apolipoproteins. A key concept is that, with their surface apolipoproteins and cholesterol core, certain lipoproteins are potential agents of atherogenesis in that they transport sterols into the artery wall.2
Estimation of the risk of CVD involves careful analysis of all standard lipid concentrations and their various ratios, and prediction of the potential presence of atherogenic lipoproteins. Successful prevention or treatment of atherosclerosis entails limiting the presence of atherogenic lipoproteins.
A new paradigm is on its way
The atherogenicity of lipoprotein particles is determined by particle concentration as well as other variables, including particle size, lipid composition, and distinct surface apolipoproteins.
Lipoproteins smaller than 70 nm in diameter are driven into the arterial intima primarily by concentration gradients, regardless of lipid composition or particle size.3 A recent Consensus Statement from the American Diabetes Association and the American College of Cardiology observed that quantitative analysis of these potentially atherogenic lipoproteins is one of the best lipid/lipoprotein-related determinants of CVD risk.4 Lipoprotein particle concentrations have emerged not only as superb predictors of risk, but also as goals of therapy.5-7
Because of cost, third-party reimbursement, varying test availability, and lack of interpretive knowledge, few clinicians routinely order lipoprotein quantification. Historically, CVD risk and goals of therapy have been based on lipid concentrations (the amount of lipids trafficked within lipoprotein cores) reported in the lipid profile. Guidelines from the National Cholesterol Education Program, Adult Treatment Panel III (NCEP ATP-III)8,9 and the American Heart Association (AHA) CVD Prevention in Women10,11 use lipid concentrations such as total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), and TG as estimates or surrogates of lipoprotein concentrations ( TABLE 1 ).