Special Testing for Cardiovascular Risk 

Advanced Lipid Tests
The usual blood test done to check “cholesterol” is called a Lipid Panel. A lipid panel is reported as 4 components:

1. Total cholesterol
2. Triglycerides
3. HDL cholesterol aka “good cholesterol”
4. LDL cholesterol aka “bad cholesterol”

These components are used routinely in general medical practice to assess risk of atherosclerosis and its complications such as heart attack, stroke, and blockages of large arteries which carry blood to the legs, kidney and various vital organs. In fact, national guidelines for the diagnosis and treatment of high cholesterol in adults, issued by the National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP), use the components of the lipid panel in their recommendations for risk assessment and treatment of high cholesterol.

Advanced Lipid Tests are blood tests which give more “cholesterol” information than the lipid panel alone. The results are used to better estimate atherosclerotic risk and to guide us in setting more precise and individualized treatment goals. Besides “cholesterol”, this category also includes blood  tests to assess so-called “novel risk factors” for atherosclerosis. Some of these tests diagnose genetic(inherited) risk factors, some assess inflammation, and some are useful aides in selecting which medications may be most effective in a particular case.

1. LDL particle number (concentration)
2. Small LDL particle number (concentration)
3. LDL particle size
4. Large HDL particle number (concentration)
5. Large VLDL particle number (concentration)

The number of LDL particles that carry cholesterol is a more important risk indicator than the amount of cholesterol in the blood. Also, the size of the LDL particles that carry cholesterol is a key factor, because smaller particles are “more risky” than larger ones. For example, a person with a certain level of LDL-cholesterol(“bad cholesterol”) is at more risk if the LDL particle number is high, compared to another person with the same level of LDL-cholesterol, but with a lower LDL particle number. The first person has a relatively high number  of smaller LDL particles compared to the lower number of larger LDL particles in the second case. In most cases, the highest priority of treatment is to lower LDL particle number.

Appropriate lifestyle modifications and medications to lower LDL particle number are the same as those used to lower LDL-cholesterol. The strategy to lower small LDL particle number, however, is often two-pronged. First, efforts are directed at lowering LDL particle number, a component of which is a variable amount of small particles.
Second, lifestyle changes and medications are prescribed to alter the size of the LDL particles, changing small particles to larger ones. Medications prescribed to increase LDL particle size are generally those used to lower serum triglycerides.

HDL particle number is measure of the “good part of the good cholesterol”. This measure is a superior predictor of CHD risk compared to the HDL-cholesterol typically reported as part of a traditional Lipid Panel. Therapeutic lifestyle change and certain medications can be employed to boost HDL particle number.

Finally, large VLDL particle number is an indicator of the level of a risky lipoprotein that carries triglycerides in the blood. Measures to address this lipoprotein are identical to those used to treat high triglycerides.

It should also be noted that the latter 3 components of the NMR LipoProfile, namely LDL particle size, large HDL particle number, and large VLDL particle number, are what are sometimes referred to as lipoprotein indicators of the metabolic syndrome. These components are sensitive to body weight, diet and activity level. Abnormalities of these three lipoprotein components are associated with an increased chance of developing type II , or adult onset, diabetes mellitus in the future.

For more information on the NMR LipoProfile,  go to www.LipoScience.com.

Lipoprotein(a)
If LDL is thought of as “bad cholesterol”, then Lipoprotein(a), or Lp(a), can be described as “very bad cholesterol”. High Lp(a) levels are strongly associated with increased risk for heart attack and stroke. Individuals with increased Lp(a) have a two fold risk of developing atherosclerosis.

Lipoprotein(a) concentrations are genetically determined, though there is recent evidence that dietary trans-fats can (likely need over one gram daily) increase Lp(a).  There are many different inherited variations of Lp(a), some higher risk than others. Lp(a) levels are reportedly higher in African Americans than in Caucasian Americans, but the kind of Lp(a) that is typically found in African Americans is usually “less risky” than that found in Caucasions.

Current data indicate that Lp(a)  is a risk marker for cardiovascular disease (CVD), rather than a risk factor, as there has been no demonstration of CVD risk reduction by lowering  Lp(a). Hence in patients with elevated Lp(a) levels, treatment should target control of  LDL cholesterol , or “bad cholesterol”, and other CVD risk factors, rather than Lp(a) per se. The LDL goal should be individualized according to a patient’s overall CVD risk, but elevated Lp(a) is an important consideration in deciding how low to treat the “bad cholesterol”. Most LDL cholesterol-lowering drugs, such as statins, are not effective in lowering Lp(a), but are used nonetheless to achieve an optimal LDL-cholesterol target.
Niacin is the only lipid-lowering medication shown to be effective in reducing Lp(a); up to 36% in some reports. Therefore niacin is often used in cases of elevated Lp(a) if statins are not tolerated, or, if a second drug is needed, in addition to a statin,  to reach a target LDL cholesterol level.

Lp(a) levels can also be influenced by a woman’s hormonal status. Both estrogen and progesterone, the two main “female hormones”, tend to decrease Lp(a) in women. Accordingly, Lp(a) may increase, sometimes dramatically, after menopause. In those cases, post-menopausal hormone replacement therapy may result in significant lowering, and sometimes normalization of, Lp(a). Indeed there are some limited data to suggest cardiovascular benefit in postmenopausal women with elevated Lp(a) who choose to take hormone replacement therapy (HRT). The decision to use HRT at menopause is, however, a very complex one. Lp(a) status is only one of many considerations in choosing whether or not to take hormone(s). The decision should be made with the counseling and advice of a qualified physician, well-versed in the multiple factors to be considered, and  familiar with the details of the patient’s personal and family medical history. This is typically the patient’s primary care physician or gynecologist.

 
Genetic Tests  

Apolipoprotein E Genotype
The apolipoprotein E (Apo E) genotype is a blood test that checks for specific, inherited, traits that could be the cause of high cholesterol, high triglycerides,and increased susceptibility to cardiovascular disease. General inheritance occurs in such a way that we posses pairs of genes for a given trait, one gene from our mother and one gene from our father. Accordingly, an individual has not one, but a pair of ApoE genes. The Apo E gene is present in three common foms: E2, E3, and E4. The E3 form is the most common (79%) in all races and popultions, followed by E4 (13%), then E2(8%). This results in the following frequencies of Apo E genotypes (pairs) in the general population:
                                       E3/E3 (63%)      E4E4 (3%)
                                       E4/E3 (18%)      E4E2 (2%)
                                       E3/E2 (13%)      E2E2 (1%)
 
An individual’s inherited Apo E pair is an important determinant of cholesterol and triglyceride levels and relative risk of atherosclerosis.

 The E4 form is associated with increased cholesterol levels and increased susceptibility to cardiovascular disease. Persons with APO E4 gene are known to be more sensitive to dietary fat and cholesterol. Studies indicate that the presence of an Apo E4 gene increases the odds of CHD by a factor of about 1.4 in men and 1.8 in women, with higher risk associated with having an Apo E4 pair. The Apo E4 variant is also a risk factor for late onset Alzheimer’s disease. One study found the following risks of Alzheimer’s disease compared to an individual with an E3/E3 pair:
                                   E4/E2 Increased risk by factor of 2.6
                                   E4/E3 increased risk by factor of 3.2
                                   E4/E4 increased risk by factor of 14.9

The E2 form is associated with high triglycerides and the E2/E2 pair can be associated with very high cholesterol/triglycerides, increased risk for cardiovascular disease, and increased risk for pancreatitis (an inflammatory condition of the pancreas which can be very serious or even fatal). Certain medications are more effective than others in treating patients with the E2/E2 variant.

Angiotensin Converting Enzyme (ACE) Genotype
The ACE gene is present in two common forms, I and D. Individuals posses a pair of ACE genes, one inherited from the mother, and one from the father. Therefore possible pairs include:
                       ACE I/I
                       ACE I/D
                       ACE D/D
 
The ACE D/D variant is associated with increased risk for coronary artery disease, heart attack, coronary restenosis after stent implantation, and blood-clotting complications after surgery. Patients with the ACE D/D pair exhibit enhanced blood pressure responses to certain medications used to treat high blood pressure.

 
Vascular Inflammation Markers 

High Sensitivity C-Reactive Protein (HS-CRP)
Half of heart attacks occur in individuals with normal or near normal cholesterol levels. Other factors, including inflammation, are involved in the development of manifest coronary heart disease. HS-CRP is a blood test that indicates the amount of inflammation in an individual’s system.

 An elevated HS-CRP , then, is an additional risk factor for heart attack. In fact, studies indicate that a person with a high HS-CRP and low “bad cholesterol”(LDL-cholesterol) is at about the same risk for a cardiovascular event as another person with low HS-CRP and high “bad cholesterol”. Therefore lifestyle interventions and drug therapies are often aimed not only at reducing cholesterol levels, but also at decreasing the level of HS-CRP.

Lipoprotein-Associated Phospholipase A2 (Lp-PLA2)
Lp-PLA2 is a promising new marker of inflammation and cardiovascular risk. Assessment of LP-PLA2 has recently become available by means of a blood test call PLAC. The PLAC test appears to be a more specific indicator of coronary inflammation than the more commonly employed HS-CRP. Whereas HS-CRP may be high because of other bodily sources of inflammation, such as arthritis, the PLAC test is more specific for vascular disease. The same therapeutic lifestyle changes and medications used to lower cholesterol and HS-CRP appear to be effective in decreasing PLAC.

Procedures

DEXA Body Composition Analysis
DEXA Body Composition Analysis (DEXA BCA) testing is considered the medical gold standard in terms of personal assessment of how your bodyfat distribution will affect your cardiovascular risk (due to different distributions of bodyfat having different cardiovascular risk even at the same total bodyfat percentage).  With the help of your UnaSource Weight Control physician, DEXA BCA is the most practical “ultra-accurate” and personalized ways to know your PERSONAL healthy weight based on bodyfat percent and distribution (the TRUE medical issues of concern).  Though not typically covered by insurance, DEXA BCA can be a great tool in guiding those who are serious about their health towards realistic and personalized goals.