The peak time for a heart attack appears to be between 6:00 AM and 12:00 noon. Fujino et al., 2001 reported that morning heart attack victims were found to have significantly higher levels of Lp(a), the only distinguishable factor compared to the other group. There was, also, a tendency toward hypercoagulation (excess clotting), increasing the risk for developing a life-threatening thrombus or clot. The conclusion of the Japanese study was that increases in Lp(a) appear to be influencing coagulation factors involved in the occurrence of morning heart attacks.
Lp(a) has a lipoprotein structure nearly identical to LDL cholesterol. A variation occurs when a disulfide bond attaches Apo(a), a protein having the nature of plasminogen, to the lipoprotein. LDL + Apo(a) = Lp(a). Plasminogen is an inactive plasma protein that is converted to its active form, plasmin (also called fibrinolysin), an agent capable of dissolving fibrin.
Because of similar structure, it is theorized that Lp(a) competes for plasminogen that binds to fibrin and the surface of endothelial cells, inhibiting the break down of fibrin. Thus it appears that Lp(a) alters fibrinolysis (the breakdown of fibrin) occurring at the cell surface and inhibits plasminogen binding to fibrin. The end result is a greater risk of blood clot formation. (Loscalzo et al., 1990)
Complicating the atherosclerotic/Lp(a) mechanism, Apo(a) has a sticky, Velcro nature, causing it to easily tie up in blood vessels. Apo(a)’s adhesiveness provides an ideal trap for LDL, VLDL, and other bloodstream infiltrates, as calcium. In layered fashion, circulating materials mount the debris, promoting the growth of an atheromatous tumor. As plaque accumulates, greater amounts of Lp(a) are observed at the site of the occlusion. Recent studies also incriminated lipoprotein(a) in angina pectoris, sighting accumulations of Lp(a) in the plaque of unstable angina patients.
The risk of a major coronary event nearly tripled among middle-aged men participating in a Lp(a) heart study, whose Lp(a) levels fell within the highest 20% of the study group compared to those with lower levels. (VonEchardstein et al., 2001) The risks escalate even higher if Lp(a) coexists with high LDL cholesterol, low HDL cholesterol, and hypertension. Investigators, also, noted elevated Lp(a), i.e., above 30 mg/dL in 20% of all thromboembolism patients, compared to 7% of healthy controls. Lp(a) may prove to be one of the most predictive of the risk factors for strokes, restenosis (recurrent narrowing of a vessel), or heart attack following either coronary bypass surgery or angioplasty.
Plaque formation is an essential response to vascular injury. When a blood vessel has been damaged, repair is paramount. If benign materials are available, as vitamin C, to protect the vessel from injury and to participate in vascular repair, the need for Lp(a) is moot. Without adequate amounts of vitamin C, Lp(a) becomes indispensable.
There is a vast difference between materials used to repair vascular injuries. For example, vitamin C repairs the wound, leaving the vessel wall smooth but stronger; Lp(a) repairs the injury, leaving residual trappings, i.e., a sticky compress, capable of continued growth. Although Lp(a) has an important function in the body, Matthias Rath, M.D., considers Lp(a) 10 times more dangerous than LDL cholesterol.
Aortic stenosis, the narrowing of the valve separating the left ventricle from the aorta, is often described as a calcification process. Lp(a) appears to play a role in this process as deposition of Lp(a) on the aortic valve creates a binding site for calcium.
According to an article in Circulation (September 5, 2000:102) research shows that people with high levels of Lipoprotein(a) or Lp(a), have a much higher risk of heart disease.
Currently, there are no available drugs to lower Lp(a), although researchers state that some research suggests estrogen therapy may help. Chee Jeong Kim, MD et al reported in the Archives Internal Medicine (1996;156:1693-1700) that 551 postmenopausal women using either estrogen with or without synthetic progestins had their Lp(a) and lipid levels measured before and 12 months after hormone replacement therapy. Estrogen replacement therapy for 12 months lowered the Lp(a) level by 37.1%. The addition of a progestagen attenuated the Lp(a)-lowering effect and the HDL (the “safe cholesterol”) raising effect. of estrogen. The low-density lipoprotein cholesterol level was decreased by 10.9% to 17.6% in all the treatment groups. Estrogen replacement therapy months raised the HDL-C level by 17.8% after 12 months. In the group with combined estradiol plus a synthetic progestin, the HDL-C level was either unchanged or raised slightly after 12 months of treatment. The researchers concluded that combined estrogen and progestagen therapy may have effects on the heart different from those of estrogen therapy alone because of adverse impact of progestogens on Lp(a) and HDL-C levels. (Reminder: Prometrium® and progesterone are not progestagen and are not synthetic!)
Studies suggest that diet can change Lp(a) levels. One study showed significant increases in Lp(a) levels of subjects consuming diets high in trans fats, but not in those consuming high levels of saturated fats (Journal of Lipid Research 1992 Oct;33(10):1493-501). Dr. Mary Enig maintains that saturated fats actually lower Lp(a) levels. In another study, researchers found a 24% reduction in Lp(a) levels with a diet high in vegetables, fruits, and nuts (Metabolism 1997 May;46:530-7). In a study published in Arteriosclerosis Thromb Vascular Biology (1999 May;19:1250-6) fish consumption was shown to reduce Lp(a) levels, most likely due to the omega-3 fatty acid content. In patients consuming large quantities of walnuts, Lp(a) levels were found to decrease an average of over 6%, as well as an almost equal decrease in LDL cholesterol levels (Annals of Internal Medicine 2000 Apr 4;132(7):538-46).
From the American Journal of Clinical Nutrition (March 1999;69:419-425)… Danish researchers discovered, however, that soy protein appears to increase lipoprotein (a) levels, which suggests that use of soy protein might not be advisable. It is known that dietary substitution of soy protein for casein decreases LDL and increases HDL cholesterol levels. However, most studies on soy have been funded by the edible oil industry that has strongly vested multi billion dollar incentives to promote soy.
Linus Pauling and fellow researcher Mathias Rath hypothesized that Lp(a) levels may be increased in some cases due to a vitamin C deficiency. They note that Lp(a) is found mostly in the blood of primates and the guinea pig, which have lost the ability to synthesize ascorbate (a component of vitamin C), but only rarely in the blood of other animals that still produce their own vitamin C. They also noted that the Lp(a) and ascorbic acid possess some similar properties, such as in the acceleration of wound healing and other cell-repair mechanisms, the strengthening of the extracellular matrix (e.g., in blood vessels), and the prevention of lipid peroxidation. Based on this, Pauling and Rath suggested that humans intentionally synthesize Lp(a) when it is lacking an adequate vitamin C.
The next question is what causes these “fat” molecules to stick to the artery wall?” The Nobel prize winning answer turned out to be Lysine (and Proline) Binding Sites (LBS for short). The Lp(a) or “cholesterol” binding sites are amino acid residues of collagen protein that becomes exposed when blood vessels “crack” and expose these LBS to the blood, which then attracts the Lp(a) molecules. The result of Lp(a) binding is to create the atherosclerotic plaque. There are well over 1000 MEDLINE (US National Medical Database) references to Lp(a). These reports confirm that Lp(a) cholesterol molecules bind to blood vessel walls via the Lysine and Proline Binding Sites forming atherosclerotic plaques and occlusive cardiovascular disease.
Linus Pauling stated in the Journal of Orthomolecular Nutrition August 1994, “Knowing that lysyl residues are what causes lipoprotein-(a) to get stuck to the wall of the artery and form plaques, any physical chemist would say at once that the thing to do is prevent that by putting the amino acid lysine in the blood to a greater extent than it is normally.” Pauling’s idea was to increase the lysine concentration in the blood serum causing Lp(a) to bind with lysine molecules in the blood (rather than on the blood vessel wall) rendering the Lp(a) inactive. The Pauling/Rath U. S. Patent # 5,278,189 is for the prevention and treatment of occlusive cardiovascular disease with vitamin C and substances that inhibit the binding of lipoprotein-(a). The patent provides a method for the prevention and treatment of cardiovascular disease, such as atherosclerosis, by administering therapeutically effective dosages of a formula composed of vitamin C, lipoprotein-(a) binding inhibitors (e.g., lysine and proline or their analogs) and antioxidants. Their treatment approach doesn’t depend on the reason the Lp(a) based plaque forms. It really doesn’t matter whether the arterial lesions were caused by mechanical stress, a vitamin deficiency, oxidized cholesterol, elevated homo-cysteine, fat in the diet, etc…
Linus Pauling and Matthias Rath discovered that substances that inhibit the binding of lipoprotein-(a) also cause lipoprotein-(a) to be released from the arterial wall. According to the patent, a binding inhibitor (e.g., lysine or lysine analog) used alone or in conjunction with ascorbate, finds Lp(a) in the blood and binds with it before the molecule can reach the walls of arteries. At high enough concentrations, the lysine in the blood attracts Lp(a) in the existing plaques and will dissolve the plaque.
AM Scanu of the University of Chicago published an article that suggested apolipoprotein(a), a component of Lp(a) rather than only Lp(a) should be emphasized along with the apolipoprotein B100, which is found mainly in low-density lipoprotein (LDL). The latter is often called the “bad” form of cholesterol to which apolipoprotein(a) and Lp(a) are linked. According to recent studies, small-size apolipoprotein(a) isoforms may represent a cardiovascular risk factor either by themselves or synergistically with plasma Lp(a) concentration. Moreover, the density properties of the LDL moiety may have an impact on Lp(a) pathogenicity. It has also become apparent that Lp(a) can be modified by oxidative events and by the action of lipolytic and proteolytic enzymes with the generation of products that promote atherosclerosis and thrombus formation. For this reason more sophisticated tests may be used to better classify risks.
The reference interval for Lp(a) is 0-30 mg/dL. Reference ranges are only valuable as generic markers. Depending upon the test, risk may be, significantly, increased as values reach upper or lower limits of normal. Rapid progression of arteriographically determined coronary artery disease has been significantly more common in subjects with Lp(a) levels higher than 25 mg/dL (Circulation 1995;91:948-950). Approximately 33% of the population have elevated levels of Lp(a) (>25 mg/dL). What should your Lp(a) levels be? According to Dr. Stephen Byrnes, ND, “Acceptable levels per dl of blood would be <10 mg. 11-24 mg/dl are borderline high; >25 are very high. If your Lp (a) levels are over 10, you need to take action at once.” Pauling stated, “If you have more than 20mg/dl of Lp(a) in your blood it begins depositing plaques causing atherosclerosis.”