FROM: www.Dr.

Angles-Cano ; Structural basis for the pathophysiology of lipoprotein(a) in the athero-thrombotic process. Braz J Med Biol Res 1997 Nov;30(11):1271-80.

Lipoprotein Lp(a) is a major and independent genetic risk factor for atherosclerosis and cardiovascular disease. The essential difference between Lp(a) and low density lipoproteins (LDL) is apolipoprotein apo(a), a glycoprotein structurally similar to plasminogen, the precursor of plasmin, the fibrinolytic enzyme.

Lp(a) has the capacity to bind to fibrin and to membrane proteins of endothelial cells and monocytes, and thereby to inhibit plasminogen binding and plasmin generation. The inhibition of plasmin generation and the accumulation of Lp(a) on the surface of fibrin and cell membranes favor fibrin and cholesterol deposition at sites of vascular injury.

Moreover, insufficient activation of TGF-beta due to low plasmin activity may result in migration and proliferation of smooth muscle cells into the vascular intima. These mechanisms may constitute the basis of the athero-thrombogenic mode of action of Lp(a).

Price KD; Price CS; Reynolds RD; Hyperglycemia-induced latent scurvy and atherosclerosis: the scorbutic-metaplasia hypothesis. Med Hypotheses 1996 Feb;46(2):119-29.

Latent scurvy is characterized by a reversible atherosclerosis that closely resembles the clinical form of this disease.

Acute scurvy is characterized by microvascular complications such as widespread capillary hemorrhaging. Vitamin C (ascorbate) is required for the synthesis of collagen, the protein most critical in the maintenance of vascular integrity.

We suggest that in latent sis ty, large blood vessels use modified LDL–in particular lipoprotein(a)–in addition to collagen to maintain macrovascular integrity. By this mechanism, collagen is spared for the maintenance of capillaries, the sites of gas and nutrient exchange.

The foam-cell phenotype of atherosclerosis is identified as a mesenchymal genetic program, regulated by the availability of ascorbate. When vitamin C is limited, foam cells develop and induce oxidative modification of LDL, thereby stabilizing large blood vessels via the deposition of LDL. The structural similarity between vitamin C and glucose suggests that hyperglycemia will inhibit cellular uptake of ascorbate, inducing local vitamin C deficiency.

de la Pena-Diaz A; Izaguirre-Avila R; Angles-Cano E; Lipoprotein Lp(a) and atherothrombotic disease. Arch Med Res 2000 Jul-Aug;31(4):353-9.

High plasma concentrations of lipoprotein (a) [Lp(a)] are now considered a major risk factor for atherosclerosis and cardiovascular disease. This effect of Lp(a) may be related to its composite structure, a plasminogen-like inactive serine-proteinase, apoprotein (a) [apo(a)].

This structure endows Lp(a) with the capacity to bind to fibrin and to membrane proteins of endothelial cells and monocytes, and thereby inhibits binding of plasminogen and plasmin formation. This mechanism favors fibrin and cholesterol deposition at sites of vascular injury and impairs activation of transforming growth factor-beta (TGF-beta) that may result in migration and proliferation of smooth muscle cells into the vascular intima.

Misra A; Risk factors for atherosclerosis in young individuals. J Cardiovasc Risk 2000 Jun;7(3):215-29.

Atherosclerosis starts in childhood, and is accelerated in some individuals. A cluster of clinical and biochemical factors constitute the risk profile for many of them, perhaps most important being metabolic insulin resistance syndrome.

Insulin resistance and its components for children and adolescents, especially obesity and dyslipidemia, are generators of hypertension, glucose intolerance and complications of atherosclerosis in adulthood. Some individuals are genetically predisposed, particularly those with the family history of such disorders.

For many subjects, there is ‘tracking’ of metabolic and lifestyle factors from early age to adulthood. Several new risk factors of atherosclerosis (e.g. level of lipoprotein (a), procoagulant state, hyperhomocysteinemia, low birth weight and adverse in-utero environment, and possibly inflammatory markers) are current and potentially future areas of research concerning children and young individuals.

Chong PH; Bachenheimer BS Current, new and future treatments in dyslipidaemia and atherosclerosis. Drugs 2000 Jul;60(1):55-93.

Nicotinic acid has been made tolerable with sustained-release formulations, and is still considered an excellent choice in elevating HDL cholesterol and is potentially effective in reducing lipoprotein(a) [Lp(a)] levels, an emerging risk factor for coronary heart disease (CHD).

Although LDL cholesterol is still the major target for therapy, it is likely that over the next several years other lipid/lipoprotein and nonlipid parameters will become more generally accepted targets for specific therapeutic interventions. Some important emerging lipid/lipoprotein parameters that have been associated with CHD include elevated triglyceride, oxidized LDL cholesterol and Lp(a) levels, and low HDL levels.


Elevated levels of Lp(a) are frequently overlooked by traditional medicine as a cause of heart disease. It is something that I screen for though on all our patients at high risk for heart disease.

Part of the reason why it is not looked for by traditional medicine is that they really do not have a good way to treat it. They have not discovered any drugs to lower Lp(a). The only thing that appears to work is the specific type of pharmacological nutrient manipulation discussed by Pauling.