Online Library: Lipoprotein (a)
Lipoprotein(a) – also called Lp(a) is a LDL (Low Density Lipoprotein) particle containing an additional adhesive protein surrounding it that is named apoprotein (a) or apo (a). Higher levels of Lp(a) have been shown to increase the risk of cardiovascular disease. Studies conducted in recent years show that high Lp(a) levels seem to more significantly increase the risk of heart disease if the blood levels of LDL is high and HDL low, and/or high blood pressure is present. Lp(a) can be measured in the blood. Conventional medicine does not have any methods or pharmaceutical drugs to lover this highly dangerous risk factor for cardiovascular disease and as such is not interested in recommending Lp(a) test as a part of a routine lipid panel. Commonly prescribed lipid-reducing drugs have little or no effect on Lp(a) concentration in the blood.
Homocysteine and Lipoprotein (a) Correlation in Ischemic Stroke Patients
Source: J Neurol Sci., 2009 June 15;281(1-2): pp.64-8.
Affiliation: Department of Medicine, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India.
Abstract: Homocysteine and Lipoprotein (a) have been recognized as risk factors for coronary heart disease. However, their role in ischemic stroke is still not defined. Therefore the present study was undertaken to evaluate their levels and relationship in patients of ischemic stroke. The study was conducted in consecutive patients admitted with a diagnosis of acute ischaemic stroke and age and sex matched healthy controls. The study involved 66 patients with ischaemic stroke (30 males, 36 females) of mean age 54.43+/-1.97 years and 72 controls (39 males, 33 females) of mean age 53.86+/-1.88 years. Serum Lipoprotein (a) levels in stroke cases and control group were 57.33+/-4.40 mg/dl and 23.46+/-1.09 mg/dl respectively, (p<0.001), (Odds Ratio=8.62). A positive correlation was also observed between Homocysteine and Lipoprotein (a) levels with Pearson's correlation coefficient of 0.75 and p-value<0.001. Raised homocysteine and serum lipoprotein (a) levels were found to be independently associated with ischemic stroke with a significant positive correlation between the two parameters. Elevated homocysteine levels may modulate the toxicity of lipoprotein (a) in ischemic stroke.
Vitamin C Intake and Apolipoproteins in a Healthy Elderly Japanese Population
Source: Prev Med., 2002 March;34(3): pp.364-9
Affiliation: Department of Public Health, Aichi Prefectural College of Nursing and Health, Togoku, Kaminshidami, Moriyama-ku, Nagoya 463-8502, Japan.
Abstract: Adequate vitamin C (AsA) intake may lower the risk of arteriosclerotic cardiovascular disease, but little is known about its influence on the progression of atherogenic disease in the elderly. This study examined whether AsA intake was associated with serum lipids, apolipoprotein A-1 (ApoA1) and apolipoprotein B (ApoB), in 680 Japanese elderly persons. The results show that there were no significant gender differences among mean serum lipids and apolipoprotein concentrations and intakes of macronutrients. AsA intake had a significant positive association with serum concentrations of high-density cholesterol and ApoA1, but an inverse association with serum concentrations of low-density cholesterol and ApoB, after adjusting for age, body mass index, total energy, and macronutrients. AsA intake was strongly inversely related to ApoA1/ApoB. The study concludes that increased AsA intake could play an important role in lipid composition and could be of potential importance in the genesis and prevention of atherogenic disease in the elderly.
Lipoprotein(a) is Associated with Coronary Heart Disease Independent of Metabolic Syndrome.
Source: Coron Artery Dis., 2008 May; 19(3): pp.125-31
Affiliation: Turkish Society of Cardiology, Istanbul, Turkey.
Abstract: The aim of this study was to assess the association between lipoprotein(a) [Lp(a)] with the likelihood of coronary heart disease and metabolic syndrome (MS) and its covariates in Turkish adults. Cross-sectional evaluation of 1309 adults, who had serum Lp(a) determinations by Behring nephelometry, and followed for a mean 1.0 year was performed. MS was defined by ATPIII criteria modified for male abdominal obesity. Mean age of the sample was 56.8+/-11.3 years. After adjustment for sex, age, and smoking status, log-transformed Lp(a) levels were associated significantly with coronary heart disease likelihood in both sexes combined [odds ratio: 1.53 (95% confidence interval: 1.06; 2.20)]. The Lp(a) mid-tertile (5-17 mg/dl), accompanied by significantly lower serum triglycerides than the two remaining tertiles, was inversely associated significantly with MS in either sex; in women, this association was independent of waist circumference. The study concludes that coronary heart disease likelihood, significantly associated with Lp(a) concentrations, is independent of MS and insulin resistance. Suggestive evidence was provided that intermediary Lp(a) concentrations, when accompanied by the presence of MS, could accelerate progression of vascular disease, especially in women.
Apheresis in Coronary Heart Disease with Elevated Lp (a): a Review of Lp (a) as a Risk Factor and Its Management
Source: Ther Apher Dial., 2007 February;11(1):pp.2-8
Affiliation: Klinikum der Universität München, Medizinische Poliklinik-Innenstadt, Munich, Germany.
Abstract: Lipoprotein (a) (Lp (a)) increases global cardiovascular risk, especially when LDL cholesterol is concomitantly elevated. Epidemiologic data show that Lp (a) concentration in plasma can be used to predict the risk of early atherogenesis in a dose-dependent manner and late stages of atherosclerosis are accelerated by elevated Lp (a). Therapeutic means to lower Lp (a) are limited. The most effective method to reduce plasma Lp (a) concentration significantly is therapeutic apheresis. Because apheresis is laborious and expensive, patients considered for this procedure should suffer from high Lp (a) concentrations, well beyond 50 mg/dL, and have manifested and progressive coronary heart disease despite maximal drug therapy. Experimental data and therapeutic results will be discussed in the present paper.
Vitamin C Supplementation Lowers Serum Low-Density Lipoprotein Cholesterol and Triglycerides: a Meta-Analysis of 13 Randomized Controlled Trials
Source: J Chiropr Med., 2008 June;7(2):pp.48-58
Affiliation: Assistant Professor, Department of Physiology and Biochemistry, National University of Health Sciences, Lombard, IL 60148.
Abstract: The purpose of this study was to provide a comprehensive meta-analysis of randomized controlled trials to investigate the effect of vitamin C supplementation on LDL and HDL cholesterol as well as triglycerides in patients with hypercholesterolemia. Thirteen randomized controlled trials published between 1970 and June 2007 were identified using Medline and a manual search. From the 13 trials, 14 separate group populations with hypercholesterolemia and who were supplemented with at least 500 mg/d of vitamin C for between 3 and 24 weeks were entered into the meta-analysis. This meta-analysis used a random-effects model; and the overall effect sizes were calculated for changes in LDL and HDL cholesterol, as well as triglyceride concentrations. The study shows that supplementation with at least 500 mg/d of vitamin C, for a minimum of 4 weeks, can result in a significant decrease in serum LDL cholesterol and triglyceride concentrations. However, there was a nonsignificant elevation of serum HDL cholesterol.
High-Dose Ascorbic Acid Decreases Cholesterolemic Factors of an Atherogenic Diet in Guinea Pigs
Source: Int J Vitam Nutr Res., 2007 March;77(2):pp.125-9
Affiliation: First Department of Propedeutic Surgery, University of Athens Medical School, Athens, Greece
Abstract: The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Thisstudy shows that high-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.
Lipoprotein (a) as a Predictor of Coronary Heart Disease: the PRIME Study
Source: Atherosclerosis. 2002 August;163(2): pp.377-84
Affiliation: Department of Atherosclerosis, INSERM UR545, Pasteur Institute of Lille, 1, rue du Professeur Calmette, France and University Lille II, France.
Abstract: Lp(a) was investigated as a CHD risk factor in the PRIME Study, a prospective cohort study which included 9133 French and Northern Irish men aged 50-59 at entry, without a history of CHD and not on hypolipidaemic drugs. During a follow-up of 5 years, 288 subjects experienced at least one CHD event (myocardial infarction (MI), coronary death, angina pectoris). Lp(a) was measured by immunoassay in all subjects on fresh plasma obtained at entry. Traditional cardiovascular risk factors such as low-density lipoproteins (LDL)-cholesterol, HDL-cholesterol, triglycerides, the presence of diabetes, hypertension or smoking were determined. Logistic regression analysis was used to evaluate Lp(a) level as a CHD risk factor after controlling for the other risk factors. Lp(a) appeared a significant risk factor (P<0.0006) in the whole cohort without between-population interaction, even if the association was not statistically significant in the Belfast sample. The relative risk (RR) of CHD events in subjects with Lp(a) levels in the highest quartile was 1.5 times that of subjects in the lowest quartile (RR: 1.56; 95% confidence intervals (CIs): 1.10-2.21). A high Lp(a) level was a risk for MI, coronary death and angina pectoris. A significant interaction term between Lp(a) and LDL-cholesterol levels, however, was found. The relative CHD risk associated with a Lp(a) level > or =33 mg/dl in comparison with Lp(a) <33 mg/dl increasing gradually from 0.82 (95% CI: 0.28-2.44) in men with LDL-cholesterol in the lowest quartile (<121 mg/dl) to 1.58 (95% CI: 1.06-2.40) in the highest quartile (>163 mg/dl). In conclusion, Lp(a) increased the risk for MI and angina pectoris, especially in men with a high LDL-cholesterol level. This study which analyzed Lp(a) level using a measurement independent of apolipoprotein (a) size on fresh plasma, has confirmed utility of Lp(a) as a predictor of CHD.
Lipoprotein (a) in a Population-Based Study: More significant in Turkish Women than Men?
Source: Anadolu Kardiyol Derg., 2005 December;5(4):pp.271-7
Affiliation: Turkish Society of Cardiology, 80630 Etiler, Istanbul, Turkey
Abstract: Serum lipoprotein(a) [Lp(a)] concentrations, determined in 665 persons in the 2003/04 survey of the Turkish Adult Risk Factor Study, were investigated in regard to distribution, determinants and relationship to cardiovascular risk factors, metabolic syndrome (MS) and coronary heart disease (CHD). Metabolic syndrome was observed in 44%, CHD in 14% of the study sample. Behring nephelometry was used for Lp(a) values measurements which were log-transformed for analyses because of skewing. Geometric mean values of Lp(a) in 286 men and 379 women, aged 55.5 +/-12.0 years, were 9.46+/-2.90 mg/dL and 10.46+/-3.00 mg/dL (p>0.2), respectively. Apart from a slight correlation with age, Lp(a) exhibited significant positive correlations with apolipoproteins A-I and B, low density lipoprotein-cholesterol (LDL-C) (r =0.15), total cholesterol, high density lipoprotein-cholesterol (HDL-C), systolic blood pressure and log C-reactive protein, and inverse ones with thyroid stimulating hormone (r =-0.25) in men, and log gamma glutamyltransferase in women. The study concludes that lipoprotein(a), the variance of which is known to be overwhelmingly due to the apo(a) isoforms, proved to have a significant inverse independent association with a measure of abdominal obesity. Lipoprotein(a) levels appeared not to be associated with risk for MS or CHD among men. In women, however, high Lp(a) levels were accompanied with an environment less prone to MS, and - without attaining significance -- tended to be associated with CHD likelihood, independent of age and MS. Further studies are warranted in this area.
Association of Fibrinogen and Lipoprotein(a) as a Coronary Heart Disease Risk Factor in Men (The Quebec Cardiovascular Study)
Source: Am J Cardiol., 2002 March 15;89(6): pp.662-6.
Affiliation: Quebec Heart Institute, Ste-Foy, Quebec, Canada.
Abstract: Fibrinogen has been prospectively found to correlate with coronary heart disease (CHD) but a similar association has not been well established for lipoprotein (a) (Lp(a)). Plasma lipids, Lp(a), and fibrinogen levels were measured in 2,125 men (aged 47 to 76 years) who were free of clinical CHD. During a 5-year follow-up period, 116 first CHD events were documented. Men with CHD were older, smoked more, had a higher prevalence of diabetes, and higher levels of systolic blood pressure, cholesterol, low-density lipoprotein cholesterol, Lp(a), and fibrinogen, and lower plasma high-density lipoprotein cholesterol levels. Only fibrinogen levels in the upper tertile of the distribution compared with the lower tertiles were associated with a significant risk of CHD (adjusted risk ratio 2.5; 95% confidence interval [CI] 1.4 to 4.2; p = 0.0010). Such an association was not observed with Lp(a). To assess a possible relation between fibrinogen and Lp(a) to the risk of CHD events, men were assigned to 1 of 4 groups according to fibrinogen median levels and a Lp(a) cut-off level of 300 mg/L: group 1: fibrinogen < 4.05 g/L and Lp(a) < 300 mg/L; group 2: fibrinogen < 4.05 g/L and Lp(a) > or =300 mg/L; group 3: fibrinogen > or =4.05 g/L and Lp(a) < 300 mg/L; and group 4: fibrinogen > or =4.05 g/L and Lp(a) > or =300 mg/L. Using group 1 as a reference, a significant risk ratio was only documented in group 4 (2.5; 95% CI 1.2 to 5.1; p = 0.0132). In this population, high fibrinogen levels associated with high Lp(a) levels significantly increased the risk of CHD.
Ascorbic Acid Protects Against Peroxidative Modification of Low-Density Lipoprotein, Maintaining Its Recognition by LDL Receptors
Source: J Nutr Sci Vitaminol., (Tokyo). 2001 February;47(1): pp.28-31
Affiliation: The Third Department of Internal Medicine, Nagoya City University Medical School, Japan.
Abstract: Peroxidatively modified low-density lipoprotein (LDL) may contribute to atherosclerotic processes; therefore, protecting LDL against peroxidation may thus reduce or retard the progression of atherosclerosis. This study evaluated the protective effects of ascorbic acid on copper-catalyzed LDL peroxidative modification. The protective effects of ascorbic acid on copper-catalyzed LDL peroxidative modification were examined by measurement of concentration of lipid hydroperoxides in LDL and by the provision of LDL cholesterol to lymphocytes via LDL receptor-mediated pathway. The measurement of concentration of lipid hydroperoxides in LDL showed that ascorbic acid inhibited peroxidative modification of LDL. Also, ascorbic acid preserved the ability of LDL to be recognized by LDL receptors in peripheral blood lymphocytes to the same extent as native LDL. These findings indicate that ascorbic acid may protect LDL against peroxidative modification, maintaining its ability to act as a ligand for LDL receptors in vivo.
Lp(a), Homocysteine and a Family History of Early Ischemic Cerebral Stroke
Source: Nutr Metab Cardiovasc Dis., 2001 October;11 Suppl 5: pp.52-9
Affiliation: Regional Center for Atherosclerosis Research, Pomeranian Academy of Medicine, 70-111 Szczecin, Al. Powstańców Wlkp. 72, Poland.
Abstract: High plasma lipoprotein(a) [Lp(a)] and homocysteine (HCY) levels are now considered to be independent risk factors for cerebro- and cardiovascular atherosclerotic occlusive disease, but little is known about the influence of Lp(a) and HCY on the early events of ischemic disease or their significance in subjects with a positive family history of ischemia. The aim of this study was to evaluate the relationship between HCY levels and the severity of ischemic cerebral stroke, and investigate whether there was a correlation between Lp(a) and HCY levels in the stroke patients and their children. The study involved 35 patients with early ischemic cerebral stroke aged 46.1 +/- 6.6 years and their 50 children aged 17.2 +/- 5.5 years. The patients were grouped on the basis of the form of the stroke (transient, progressive or complete stroke), and their levels of Lp(a), HCY, uric acid (UA), fibrinogen (Fb) and factor VII (FVII) activity were measured. The results show that HCY and Lp(a) concentrations increased with the severity of the ischemia, being highest in the patients with complete stroke (15.1 +/- 2.9 mumol/L and 32.9 +/- 37.6 mg/dL respectively). A similar trend was found in the offspring, with the highest HCY and Lp(a) values in the children of complete stroke patients (12.6 +/- 4.4 mumol/L and 23.0 +/- 24.6 mg/dL). Correlations between Lp(a) and HCY (r = 0.47 p < 0.05) and Fb and FVII (r = 0.60 p < 0.01) were found in the children. Multiple regression analysis revealed that only Lp(a) and Fb significantly influenced HCY levels in the offspring with a positive family history. The study concludes that HCY levels correlate with the severity of ischemic cerebral stroke and, in families with a history of ischemic cerebral stroke, the levels of the risk factors in children are determined by the levels in their parents.
Elevated Levels of Lipoprotein(a) are Present in Subjects with Early Ischemic Cardiopathy and with a Familial History of Ischemic Cardiopathy
Source: Minerva Med., 1999 May-June; 90(5-6): pp.151-8.
Affiliation: Dipartimento di Medicina Interna e Terapia Medica, Università degli Studi, Messina.
Abstract: Since the Lp(a) levels are genetically determined and fairly stable in the course of life and a family history appears to be an independent risk factor of cardiovascular diseases, this study evaluated the behavior of Lp(a) levels in patients with early events of coronary heart disease (CHD) and also in subjects with positive family history of ischemic heart diseases. The levels of lipoprotein (a) [Lp(a)] were measured in 254 subjects, 138 males and 116 females with an average age of 48.6 +/- 13.8 years (range 20-76 years). The results show that the levels of Lp(a) were higher (p < 0.01) in women (25.1 +/- 28.3 mg/dl) compared to men (17.6 +/- 18.4 mg/dl), without differences in relation to age. Fifteen of the 40 subjects with CHD had an early onset of CHD (before 50 years of age) and only in such patients the Lp(a) levels were significantly greater compared to controls (35.8 +/- 33.2 mg/dl vs 20.3 +/- 22.8 of the controls, p < 0.01), independently of other variables (age, BMI, smoking, hypertension, cholesterol, triglycerides, HDL-c, LDL-c, fibrinogen). Furthermore the Lp(a) plasmatic levels were higher in subjects with a family history of CHD (28.3 +/- 27.6 mg/dl vs 16.3 +/- 18.6 mg/dl of the subjects without a family history of CHD, p < 0.01) even if they had or not had a previous coronary ischemic event. The study concludes that such data confirms the importance of high levels of Lp(a) above all for the early events of CHD and for the subjects with a family history of CHD, which could be expression of a greater predisposition for cardiovascular events.
A New Era in Medicine
Source: Journal of Orthomolecular Medicine, 1993, 8: pp. 134-135.
Abstract: “Health care and medicine in the 21st century will significantly differ from the present: Nutritional medicine will be an essential part of any future health care system. My discovery of the Ice Age - vitamin deficiency - cardiovascular disease connection will eventually lead to the eradication of heart attacks, strokes and related cardiovascular diseases. My earlier publications in the Journal of Orthomolecular Medicine triggered repeated interest in the history of these discoveries. Thus, a brief personal chronology may be in order: In 1987, after having discovered the lipoprotein(a)-vitamin C connection I recommended vitamin C supplementation to an individual with high lipoprotein(a) levels. This marks the first therapeutic attempt to lower elevated blood concentrations of this risk factor by using vitamin C. During my research project at Hamburg University I used L-lysine and synthetic lysine analogs to isolate lipoprotein(a) from blood and from arterial walls. This suggested the therapeutic use of lysine and synthetic lysine analogs, a therapeutic technology for which I received patents in the meantime. In early 1990, after the prominent role of lipoprotein(a) in human atherosclerosis was established, I came to the United States to work on the physiologic role of lipoprotein(a) as well as to pursue my earlier therapeutic discoveries. My scientific discoveries over the year were primarily published in the Journal of Orthomolecular Medicine and I had generally invited my former colleague Linus Pauling to join me as co-author.”
Unified Theory of Human Cardiovascular Disease Leading the Way to the Abolition of This Disease as a Cause for Human Mortality
Source: Journal of Orthomolecular Medicine, 1992, 7: pp. 5-15.
Abstract: “In contrast to current therapeutic approaches, which target individual pathomechanisms or specific risk factors for CVD, this paper proposes a unified pathogenetic and therapeutic approach based on genetic, metabolic, evolutionary and clinical evidence - ascorbate deficiency. Chronic ascorbate deficiency leads to loosening of the connective tissue in the vascular wall and compensatory deposition of Lp(a) (lipoprotein(a)) and fibrinogen/fibrin.”
Solution to the Puzzle of Human Evolution (1992)
Source: Journal of Orthomolecular Medicine, 1992, 7: pp.73-80.
Abstract: “This article discusses the rationale for the proposal that the underlying genetic precondition for the evolution of man was the loss of endogenous ascorbate production about 40 million years ago. This genetic mutation became the basis of the dramatic acceleration of human evolution and a quadruplication of the brain size in the recent 2.5 million years. Scurvy, the greatest threat to evolutionary survival of ascorbate-deficient man during the Ice Age, led to survival genetic features: Lp(a) for stabilizing the vascular wall and apo(a) to increased brain size, intelligence and fertility.”
Solution to the Puzzle of Human Cardiovascular Disease: Its Primary Cause Is Ascorbate Deficiency, Leading to the Deposition of Lipoprotein(a) and Fibrinogen/Fibrin in the Vascular Wall
Source: Journal of Orthomolecular Medicine, 1991, 6: pp.125-134.
Abstract: “This article proposes that human cardiovascular disease is primarily a degenerative disease, resulting from the accumulation of lipoprotein(a), which is increased by low ascorbate concentrations. Ascorbate deficiency results from the inability of humans to synthesize endogenous ascorbate combined with an insufficient dietary ascorbate intake. Chronic ascorbate deficiency leads to extracellular accumulation of lipoprotein(a) and fibrinogen/fibrin, the hallmarks of the atherosclerotic lesion.”
Lipoprotein (a) Is a Surrogate for Ascorbate
Source: Proceedings of the National Academy of Sciences, 1990, 87: pp.6204-6207.
Abstract: “The concept that lipoprotein(a) is a surrogate for ascorbate is suggested by the fact that this lipoprotein is found generally in the blood of primates and the guinea pig, which have lost the ability to synthesize ascorbate, but only rarely in other animals. Properties shared with ascorbate, in accordance with this hypothesis, are the acceleration of wound healing and of cell repair mechanisms, strengthening of extracellular matrix (as in blood vessels), and prevention of lipid peroxidation. Evidence supporting this hypothesis is discussed.”
Immunological Evidence for the Accumulation of Lipoprotein(a) in the Atherosclerotic Lesion of the Hypoascorbemic Guinea Pig
Source: Proceedings of the National Academy of Sciences, 1990, 87: pp. 9388-9390.
Abstract: “Atherosclerosis was induced in three guinea pigs by dietary ascorbate depletion. Using SDS/PAGE and subsequent immunoblotting, Lp(a) was identified as accumulating in the atherosclerotic plaque. Furthermore, adequate amounts of ascorbate (40 mg/kg body weight/day) prevented development of atherosclerotic plaques and accumulation of Lp(a). Guinea pigs were chosen for this study as, similar to humans, they lack endogenous ascorbate production.”
Detection and Quantification of Lipoprotein (a) in the Arterial Wall of 107 Coronary Bypass Patients
Source: Arteriosclerosis, Vol. 9, No 5, September/October1989
Abstract: “The aim of this study was to investigate a possible accumulation of apo(a) in the arterial wall depending on serum Lp(a) concentrations and to compare these data to the relation between serum and arterial wall apo B. We did that by quantifying apo(a), apo B, and lipids in fresh arterial wall tissue. With these experiments, we wanted to determine whether Lp(a) is an independent risk factor for CHD. In conclusion, this is the first study showing a positive correlation of Lp(a) serum levels with apo(a) and apo B accumulation in the arterial wall. Also, the presence of intact apo (a) and Lp(a)-like particles in human arterial wall was demonstrated for the first time. We assume that in earlier studies on LDL-like particles in the arterial wall, the apo(a) might have been missed and, at least partly, Lp(a)-like particles might have been isolated. Our studies imply that Lp(a) enters the arterial wall and accumulates extracellularly, where apo(a) and apo B can be co-localized with immunohistochemistry. Further studies are necessary to define the way by which Lp(a) enters the vessel wall.”