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Does Lactic Acidosis Cause Coronary Artery Calcification?

by Carlos ETB Monteiro(more info)

listed in heart, originally published in issue 259 - January 2020


Abstract
Coronary artery calcification is highly prevalent in patients with coronary heart disease and is associated with an increase in major adverse cardiovascular events. It may also have prognostic significance for individuals with no evidence of coronary disease. Various studies have shown that the process of arterial calcification shares some features with skeletal bone formation, including chondrocyte and osteoblast differentiation, mineralization, as well as bone matrix deposition and resorption. It had been suggested over five decades ago that the body draws minerals from the bones to neutralize the effects of an acid ash diet. We propose that an increase in lactic acid/lactate production is a more important and unappreciated cause of atherosclerosis and coronary artery calcification. We will also discuss the risk factors that influence both bone loss and atherosclerosis that leads to coronary calcification, such as age, diabetes, hypertension, tobacco smoking, chronic kidney disease, rheumatoid arthritis and air pollution. In addition, warfarin, statins, metformin and other drugs can influence lactic acidosis that then leads to osteoporosis and coronary calcification. There is also good evidence that acidosis may be responsible for calcification in the aortic valve, brain and other tissues.

Introduction
Coronary artery calcification (CAC) is widespread in patients with coronary heart disease (CHD), and although previously considered a benign, asymptomatic, and age-related trait, it is now believed to be an active process that can result in atherosclerosis. Calcification forms within the intimal layer of the arterial wall and begins with spotty minuscule deposits that coalesce to form larger sheet-like accumulations that are readily visible on radiography, computed tomography and intravascular imaging.[1] Because there is a strong correlation between the extent of calcification and the degree of atherosclerosis, it has now been proposed that CAC may be the most accurate way to predict future cardiac events, especially in asymptomatic individuals.[2-4] The prevalence of CAC is age and gender related, since it occurs in more than 90% of men and 67% of women over the age of 70 years.[4]

Vascular calcifications can be classified into 2 separate types depending on whether they are located within the intimal or medial layer. Medial arterial calcification primarily affects the legs, and is prevalent in patients with peripheral vascular disease. Intimal calcification predominates in coronary vessels, and both types can be found in the carotid arteries.[5,6] The progression of medial arterial calcification is associated with renal failure, hypercalcemia, hyperphosphatemia, and parathyroid hormone. These abnormalities are not seen with intimal coronary calcification although both types of calcification share some risk factors, most of which are age related, as shown in Figure 1.

Figure 1: From Vos A et al[6]

Figure 1: From Vos A et al[6]


Table 1: Modified from Goodman et al. [7]
Table 1: Modified from Goodman et al. [7]



There is no treatment to prevent arterial calcification or its progression, which is not surprising, since the cause is not clear. There are no satisfactory animal models, because in contrast to humans, rodents, rabbits and dogs do not spontaneously develop atherosclerosis with age. Patients with end stage renal disease or uremia also have increased coronary artery calcification[8] Calciphylaxis is a rare disorder that causes subcutaneous vascular calcification and cutaneous necrosis.  It is sometimes called calcific uremic arteriolopathy, since it also usually occurs in patients with severe kidney disease. Little is known about its etiology and pathogenesis other than more than 50 percent of those affected die within 12 months after the diagnosis is made. It was first described in 1898 by Bryant and White,[9] but it was not until 1962 that the term “calciphylaxis” was coined by Hans Selye. He defined it as a hypersensitivity disorder, since in his experimental animal model, it was necessary to administration both a “sensitizer” and a “challenger” to produce calcification in various structures.[10,11] Arterial calcification has been induced in rabbits and other herbivores with extremely elevated cholesterol levels due to a very high fat diet because cholesterol is a foreign substance for them and can elicit an inflammatory response. However, these lesions are mainly in the aorta and large arteries rather than the coronaries, differ under the microscope from atherosclerotic plaque in humans, and the identical high fat diet produces no lesions in carnivorous animals. Severe fat restriction and intensive statin therapy to lower cholesterol or LDL did not prevent or diminish coronary calcification in one study,[12] and in another review of over 1,000 patients with high calcium artery calcification scores who were randomized to receive a statin or a placebo, LDL was lowered in the treatment group but there was no reduction in coronary calcification progression.[13]

The severity of coronary artery calcification is usually assessed by ultrafast computerized tomography that measures the degree of density multiplied by the area of the coronary calcification to provide a calcium artery calcification (CAC) or Agatston score, after its originator.[14] The CAC score is an independent risk marker for cardiac events, cardiac mortality, all-cause mortality, provides prognostic information and helps to identify diabetics and others at greatest risk who could benefit from screening for silent ischemia and may require more aggressive treatment.[15] It has been suggested that the process of arterial intimal calcification shares some features with skeletal bone formation, including chondrocyte and osteoblast differentiation, as well as bone matrix deposition and resorption. In addition, a variety of bone related proteins have been identified in calcified arteries,[16,17] and calcium is in the form of calcium phosphate in both bone and arteries.[18] The extent of coronary artery calcification is a better indication of the degree of atherosclerotic plaque than a reduction in lumen,[19] and is also associated with an increase in all-cause mortality [20] It is believed that spotty and incomplete calcification is more likely to cause major adverse cardiac events because of unstable and vulnerable plaque, whereas extensive calcification is more stable.[21] Since statins increase calcification,[22,23] it has been proposed they would benefit patients by making plaque more stable via some pleiotropic effect, since it is not related to lowering cholesterol or LDL.[24] This creates a conundrum for clinicians, since high calcium artery scores are associated with an increased risk of heart attacks and deaths, and no benefits have been found with statins or other cholesterol lowering drugs.

The first clue that calcification might be due to acidosis came in 2006, during the development of the Acidity Theory of Atherosclerosis.[25] Numerous articles that had been retrieved led to the hypothesis there was a link between osteoporosis and atherosclerosis, as explained in my 2012 book Acidity Theory of Atherosclerosis: New Evidences [25] as follows:

Although the prevalence of both atherosclerosis and osteoporosis increase with age, evidence that has accumulated since these initial studies[26,27] suggest a more direct relationship between these two disorders. This is supported by other studies that show an increase in carotid intima-media thickness, a marker for atherosclerosis in women who develop osteoporosis.[28,29]

Hip fracture, a frequent complication of osteoporosis, is two to five times more common in patients with heart disease than in those with no history of cardiovascular problems.[30]  Other studies have shown that bisphosphonates not only decreased the progression of osteoporosis, but also inhibited the development of atherosclerosis, in addition to reducing  total mortality.[31]  In that regard, it is important to note that bisphosphonates also reduce the production of lactic acid,[32] which further supports the hypothesis that lactic acidosis may be involved in the etiology and pathogenesis of coronary heart disease.[33]  This also substantiates the role of stress in coronary atherosclerosis, since chronic stress increases lactate.[34]

Studies Linking Acidosis to Bone Loss

“Life is a struggle, not against sin, not against the Money Power, not against
malicious animal magnetism, but against hydrogen ions" - H.L. Mencken[35]

In commenting on Mencken’s statement 75 years later, Kraut and Coburn wrote, “These words, about the meaning of life and death, may also apply to the struggle of the healthy skeleton against the deleterious effects of retained acid.”[36] It had been known since the early 20th century, that systemic acidosis causes depletion of the skeleton, an effect assumed to result from physico-chemical dissolution of bone mineral. And, as noted previously, coronary calcification is no longer viewed as a benign, asymptomatic, age-related trait, but an active process that can predict risk of coronary atherosclerosis and calcification.[37]

In 1918, Kingo Goto, at the Rockefeller Institute for Medical Research, showed that feeding acid to rabbits resulted in depletion of skeleton minerals [38] This paper also includes an excellent review of pertinent 19th century publications. More recent reports over the last two decades suggest that even subtle chronic acidosis can cause appreciable bone loss if prolonged.[39] In 1968, Wachman and Bernstein postulated that bone mineral functioned as a mechanism to buffer the fixed acid load imposed by the digestion of an “acid ash” diet in man.[40]  

Lactic Acidosis Is Associated With Coronary Disease And Atherosclerosis

However, not everyone agrees,[41] and our alternative hypothesis is that autonomic dysfunction results in an increased secretion of catecholamines that accelerates glycolysis and raises lactic acid and lactate concentration in blood and tissues for the following reasons.

a.    In advanced plaques the existence of hypoxic areas in the arterial wall – with accumulation of lactic acid in atherosclerotic lesions – appears to be related to a decreased oxygen diffusion capacity and increased oxygen consumption by foam cells.[42]
b.    Macrophages and lymphocytes convert most of their glucose into lactate rather than oxidizing it completely to CO2, and macrophages possess a selective transporter in their plasma membranes for lactic acid. This lactic acid may make the extracellular space surrounding macrophages acidic in atherosclerotic lesions.[43]
c.    It has been demonstrated that approximately two-thirds of atherosclerotic plaques show lactate dehydrogenase isoenzyme shifts significantly above that of the media and intima.[44]  
d.    The association of increased lipid levels with abnormal lactate metabolism might provide a useful screening test for the detection of coronary artery disease.[45]
e.    Plasma lipid abnormalities and myocardial lactate production were significantly associated with subsequent arteriographic progression of coronary artery disease.[46]
f.    The amount of lactate released by the myocardium has been shown to be related to the severity of coronary artery disease.[47]
g.    Lactate levels are strongly associated with increased carotid atherosclerosis and the association is independent of traditional cardiovascular risk factors.[48]

Risk Factors For Atherosclerosis That Are Associated With Lactic Acidosis, Bone Loss And Coronary Artery Calcification

Age

1.    Lactic acidosis[49,50]
2.    Bone loss[51]
3.    Coronary artery calcification[52]

Increased brain lactate is the hallmark of ageing, which is associated with an elevation of brain lactate due to effects on lactate dehydrogenase.[49] In that regard, a 1989 study designed to obtain normal blood chemistry references in elderly subjects, reviewed pertinent laboratory data from 1822 male and 1870 females.  The values for most analyses except inorganic phosphorus and total protein were significantly higher in males than female when compared to subjects aged 21 to 50, The values for lactic dehydrogenase, albumin, sodium, and calcium were higher in females older than 50 years of age than in their counterpart. When males and females were combined, the normal reference ranges for lactic dehydrogenase, alkaline phosphatase, uric acid, blood urea nitrogen, creatinine and potassium tended to be elevated, while those for total protein, albumin and calcium declined with aging.[50] In the aging skeleton, bone volume and mass declines in both sexes and in people of all ethnic backgrounds, and is often associated with osteoporosis and an increased risk of fracture.[51]

As Leopold noted, “Vascular calcification, once considered a passive consequence of aging, is now recognized to be a highly regulated process akin to bone formation. Vascular calcification is prevalent across ethnicities and age groups and observational studies show an interaction with aging in asymptomatic adults and in individuals with established coronary artery disease.” [52]

Diabetes

1.    Lactic acidosis[53-55]
2.    Bone loss[56-58]
3.    Coronary artery calcification[59]
As noted in a 2016 study, “Elevated circulating lactate is a common occurrence in diabetes patients and this finding suggest it may contribute to the increased prevalence of vascular calcification in this population.” [53]

Hypertension

1.    Lactic acidosis[60]
2.    Bone loss[61]
3.    Coronary artery calcification[62,63]

Smoking

1.    Lactic acidosis[64,65]
2.    Bone loss[66]
3.    Coronary artery calcification[67]

Chronic Kidney Disease

1.    Lactic acidosis [68,69]
2.    Bone loss [70]
3.    Coronary artery calcification [71,72]

High Carbohydrate Diets

1.    Lactic acidosis [73-75]
2.    Bone loss [76]
3.    Coronary artery calcification [77,78]

“High levels of sugar-sweetened carbonated beverage consumption may be associated with a higher prevalence and degree of CAC in asymptomatic adults without a history of cardiovascular disease, cancer, or diabetes.” [77]
“Diets low in carbohydrate and high in fat and/or protein, regardless of the sources of protein and fat, were not associated with higher levels of CAC, a validated predictor of cardiovascular events, in this large multi-ethnic cohort.“ [78]

Rheumatoid Arthritis

1.    Lactic acidosis [79]
2.    Bone loss [80,81]
3.    Coronary artery calcification [82,83]

Air Pollution

1.    Lactic acidosis[84]
2.    Bone loss[85]
3.    Coronary artery calcification[86]

Drugs that are associated with lactic acidosis, bone loss and coronary artery calcification

Warfarin

1.    Lactic acidosis [87]
2.    Bone loss [88]
3.    Coronary artery calcification [89]

Metformin

1.    Lactic acidosis[91-93]
2.    Bone loss[94]
3.    Coronary artery calcification[95]

Several older studies showed that metformin was osteogenic in vitro. In contrast, recent research found no effect of metformin on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells. And a 2015 report on forty postmenopausal diabetic women found that metformin is neither osteogenic nor did it have anti-osteoporotic effects.[94] A more recent report found that there were no CAC differences between lifestyle and placebo intervention groups in either sex. CAC severity and presence were significantly lower among men in the metformin versus the placebo group (age-adjusted mean CAC severity.[95] However, according to the authors, there are several limitations in their study, since “Interpretation of the effect of the interventions was based on the assumption that there were no differences in baseline CAC given the randomization of subjects into intervention groups at baseline.” In addition, “We found no differences in cardiometabolic risk factors at baseline between treatment groups except for slightly lower HDL-C and higher smoking rates in women in the placebo group only”, and concluded that “Whether these findings translate into beneficial effects on CVD events will require follow-up”[95]

Statins

1.    Lactic acidosis [96-98]
2.    Bone loss [99, 117]
3.    Coronary artery calcification [100]

The 2015 JUPITER Trial in men and women with evidence of inflammation concluded that randomization to rosuvastatin did not reduce the risk of fracture and that, higher baseline high sensitivity C-Reactive Protein was not associated with an increased risk of fracture.[99] This is consistent with other statin trial results. The authors also state, “Baseline use of thiazide diuretics, bisphosphonates, calcium, vitamin D, and inhaled or oral steroids did not result in a change in effect estimates and thus were omitted from the multivariate model.”[99] However, it is important to emphasize that bisphosphonates reduce the increased production of lactic acid caused by statins, therefore offsetting their negative effects, which could have influenced the JUPITER statistics and conclusions.

A 2016 study[100] found that statin intake in subjects with an LDL cholesterol equal or greater than 115 milligrams per deciliter, was associated with lower CAC progression than statin intake in subjects with LDL cholesterol levels below 115 mg/dL. But guidelines suggest that individuals with an optimal LDL-C at or below 100 mg/dL have lower rates of heart disease and stroke, and some claim that LDL-C should be lowered as much as possible. This could pose a perplexing problem for physicians when prescribing statins.

A study published in 2019 concluded that the diagnosis of osteoporosis in statin-treated patients is dose-dependent[117]
The acidity theory of atherosclerosis theory may be helpful in this regard, because of the following findings.

a.    Lowering pH augments the oxidation of low-density lipoprotein (LDL) by releasing iron and copper radicals, and decreasing anti-oxidant defenses.[101,102]
b.    LDL oxidation occurs within lysosomes in macrophages of atherosclerotic lesions rather than the surrounding interstitial fluid. Most importantly, studies have shown that this oxidative process can be promoted by an acidic pH, and is inhibited by chloroquine, which increases lysosome pH. [103]

Coronary Artery Calcium is Associated With An Increase In Major Adverse Cardiovascular Events Over The Next 3 Months

A study presented at the American College of Cardiology Scientific Session on March 16, 2019, reported that patients whose scans revealed significant CAC scores were at higher risk of a cardiac event within 90 days compared with controls whose scans showed no CAC. The study involved 5,547 symptomatic patients without a history of coronary artery disease or elevated troponin, who underwent Rb-82 cardiac PET/CT scans from April 2013 to July 2016. CAC was associated with a statistically significant higher risk of 90-day coronary angiography, high-grade obstructive CAD, revascularization and long-term major adverse coronary events (p<0.0001).[104]

It is important to recognize that the heart is an organ that is always active and never rests, in contrast to other muscles in the body. Chronic or acute elevations of catecholamines can accelerate myocardial glycolysis and result in a significant increase in lactate production during coronary events.[105]

Stroke, Acidosis and Coronary Artery Calcification

Acidosis is also a hallmark of stroke[106] and the presence and severity of coronary artery calcification is an independent predictor of future stroke events in the general population.[107,108]

Cancer, Acidosis and Coronary Artery Calcification

Acidosis is another hallmark of cancer,[109] and the 2015 Multi-Ethnic Study of Atherosclerosis trial demonstrated an increase in the incidence of coronary artery calcification over time in individuals with cancer compared with non-cancer controls.[110] This relationship persisted even when other risk factors for atherosclerosis were excluded. A subsequent 2018 study revealed that cancer chemotherapy can also worsen CAC.[111] In that regard, it is important to note that Cisplatin, a popular chemotherapy drug in use for over four decades has recently been shown to cause acidosis.[112]
Conclusion

We have tried to demonstrate and explain how lactic acidosis increases coronary artery calcification and why various drugs and other factors also influence this process. Long-term and high dose statin therapy increase coronary artery calcification, which poses a problem for practitioners.[113] Statin proponents claim that spotty and incomplete calcification is more likely to cause major adverse events and that statins stabilize vulnerable plaque.[114] They also propose that PCSK9 inhibitors suppress coronary artery calcification by regulation of inflammation.[115]
However, we concur with A. Arbeb-Zadah and V. Fuster’s conclusion that:

“Despite major advancements in coronary artery imaging and identification of atherosclerotic lesion morphology associated with rupture, there is no conclusive evidence that individual plaque assessment better predicts acute coronary event risk than established risk factors, such as the extent and severity of coronary artery disease. Pathology and clinical studies consistently demonstrate that atherosclerotic plaques rupture without clinical symptoms much more frequently than is widely acknowledged, challenging the notion of a close association between plaque rupture and clinical events.”[116]

In addition to coronary artery calcification, lactic acidosis may also cause calcification in the aortic valve, brain, and other tissues.

The introduction of this article was developed by Prof. Dr. Paul J. Rosch, Chairman from The American Institute of Stress,  to whom I dedicate our present postulation on lactic acidosis as cause of coronary artery calcification, noting that this is not the first time I have been inspired by this brilliant teacher and researcher.

The postulation contained in the present article was first introduced during my lecture on March 27 at the “Fifth International Congress for Advanced Cardiac Sciences. King Of Organs, 2019”, occurred in Saudi Arabia (Schedule at https://bit.ly/2G5U3xe )

References

1. Mori H. Torii S et al. Coronary Artery Calcification and its Progression - What Does it Really Mean? JACC Cardiovasc Imaging, 11(1):127-142: 2018 at https://www.sciencedirect.com/science/article/pii/S1936878X1731001X?via%3Dihub

2. Greenland P, LaBree L, Azen SP, et al. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA, 291:210–215; 2004 at https://jamanetwork.com/journals/jama/fullarticle/197989

3. Demer LL, Tintut Y. Vascular calcification: pathobiology of a multifaceted disease. Circulation, 117;2938–2948: 2008 at https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.107.743161

4. Wong ND, Kouwabunpat D, Vo AN, et al. Coronary calcium and atherosclerosis by ultrafast computed tomography in asymptomatic men and women: relation to age and risk factors. Am Heart J 127:422–430: 1994 at https://www.sciencedirect.com/science/article/pii/0002870394901333

5. Liu WW, Zhang Y, Yu C-M et al. Current understanding of coronary artery calcification. J Geriatr Cardiol, 12(6): 668–675: 2015. doi: 10.11909/j.issn.1671-5411.2015.06.012 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712374/

6. Vos A, Kockelkoren R, de Vis JB, van der Schouw YT et al. Risk factors for atherosclerotic and medial arterial calcification of the intracranial internal carotid artery. Atherosclerosis, 276:44-49: 2018 at https://www.atherosclerosis-journal.com/article/S0021-9150(18)31204-8/fulltext

7. Goodman WG, London G, Amann K, et al. Vascular calcification in chronic kidney disease. Am J Kidney Dis, 43:572–9: 2004 at https://www.ajkd.org/article/S0272-6386(03)01583-X/fulltext

8. London GM. Cardiovascular Calcifications in Uremic Patients: Clinical Impact on Cardiovascular Function. JASN,14 (suppl 4): S305-S309; 2003 DOI: https://doi.org/10.1097/01.ASN.0000081664.65772

9Bryant JH, White WH. A case of calcification of the arteries and obliterative endarteritis, associated with hydronephrosis, in a child aged six months. Guys Hosp Rep. 55:17–20: 1898 at https://archive.org/details/b22411811/page/18

10Selye H, Gabbiani G, Strebel R. Sensitization to calciphylaxis by endogenous parathyroid hormone. Endocrinology, 71:554–558: 1962 at https://academic.oup.com/endo/article-abstract/71/4/554/2702892?redirectedFrom=fulltext

11. Selye H. The dermatologic implications of stress and calciphylaxis. J Invest Dermatol. 39:259–275: 1962.

12. Houslay ES, Cowell SJ, Prescott RJ, et al. Progressive coronary calcification despite intensive lipid lowering treatment: a randomised controlled trial. Heart, 92:1207–12: 2006 at https://www.jidonline.org/article/S0022-202X(15)49748-9/pdf

13Arad Y, Spadaro LA, Roth M, Newstein D, Guerci AD. Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized clinical trial. J Am Coll Cardiol 46:166–72: 2005 at https://www.sciencedirect.com/science/article/pii/S0735109705010326?via%3Dihub

14.  Agatston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 15:827–832: 1990 at https://www.sciencedirect.com/science/article/pii/073510979090282T?via%3Dihub

15. Neves PO, Andrade J, Monção H. "Coronary artery calcium score: current status". Radiologia Brasileira, 50 (3): 182–189: 2017 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487233/

16. Dhore CR, Cleutjens JP, Lutgens E. et al. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol, 21:1998-2003: 2001 at https://www.ahajournals.org/doi/full/10.1161/hq1201.100229

17Roijers RB, Debernardi N, Cleutjens JP et al. Microcalcifications in early intimal lesions of atherosclerotic human coronary arteries. Am Pathol, 778 : 2879- 87: 2011 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124018/

18Schmid, K., McSharry, W.O., Pameijer, C.H., and Binette, J.P. Chemical and physicochemical studies on the mineral deposits of the human atherosclerotic aorta. Atherosclerosis. 37: 199–210: 1980 at https://www.atherosclerosis-journal.com/article/0021-9150(80)90005-2/fulltext

19Sangiorgi, G., Rumberger, J.A., et al. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using non decalcifying methodology. J Am Coll Cardiol. 31: 126–13: 1998 at https://www.sciencedirect.com/science/article/pii/S0735109797004439

20.  Budoff M.J., Hokanson J.E., Nasir K., et al) Progression of coronary artery calcium predicts all-cause mortality. J Am Coll Cardiol  3:1229–1236: 2010 at https://www.sciencedirect.com/science/article/pii/S1936878X10006996

21.   Kataoka Y, Wolski K, Uno K. et al. Spotty calcification as a marker of accelerated progression of coronary atherosclerosis: insights from serial intravascular ultrasound. J Am Coll Cardiol. 59:1592–1597: 2012 at https://www.sciencedirect.com/science/article/pii/S073510971200959X

22.  Saremi A., Bahn G., Reaven P.D., for the VADT Investigators. Progression of vascular calcification is increased with statin use in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care, 35:2390–2392: 2012 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3476911/

23.  Puri R., Nicholls S.J., Shao M., et al. Impact of statins on serial coronary calcification during atheroma progression and regression. J Am Coll Cardiol 65:1273–1282: 2015 at http://www.onlinejacc.org/content/65/13/1273

24.  Madhavan MV, Tarigopula M, Mintz GS et al. Coronary Artery Calcification: Pathogenesis and Prognostic Implications. Journal of the American College of Cardiology, 63:1703-14: 2014 at https://www.sciencedirect.com/science/article/pii/S0735109714003283

25.  Monteiro ETB C. “Acidity Theory of Atherosclerosis – New Evidences”, 2012 at https://www.amazon.com/Acidity-Theory-Atherosclerosis-New-Evidences/dp/1469934760

26.  Dent CE, Engelbrecht HE, Godfrey RC. Osteoporosis of lumbar vertebrae and calcification of abdominal aorta in women living in Durban. Br Med J. 4:76-79: 1968 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1912153/

27.  Fujita T, Okamoto Y, Sakagami Y, et al. M. Bone changes and aortic calcification in aging inhabitants of mountain versus seacoast communities in the Kii Peninsula. J Am Geriatr Soc. 32:124- 128: 1984 at https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1532-5415.1984.tb05852

28.  Tamaki J, Iki M, Hirano Y, et al. Low bone mass is associated with carotid atherosclerosis in postmenopausal women: The Japanese Population-based Osteoporosis (JPOS) Cohort Study. Osteoporosis International, 20: 53-60: 2009 at https://link.springer.com/article/10.1007%2Fs00198-008-0633-z

29.  Sumino H. Kasama S, Ichikawa S, et al. Relationship between Carotid Atherosclerosis and Lumbar Spine Bone Mineral Density in Postmenopausal Women. Hypertension Research. 31:1191–1197: 2008 at https://www.nature.com/articles/hr2008151  

30.  Sennerby U, Melhus H, Gedeborg R et al. Cardiovascular Diseases and Risk of Hip Fracture, JAMA. 302(15):1666- 1673: 2009 at https://jamanetwork.com/journals/jama/fullarticle/184740

31.  Lyles KW, Colón-Emeric CS, Magaziner JS, et al; HORIZON Recurrent Fracture Trial. Zoledronic acid. and clinical fractures and mortality after hip fracture. N Engl J Med. 357(18):1799-1809: 2007 at https://www.nejm.org/doi/full/10.1056/NEJMoa074941

32.  Bell NH, Johnson RH. Bisphosphonates in the treatment of osteoporosis, Endocrine, 6:203-206: 1997 at https://link.springer.com/article/10.1007%2FBF02738966

33. Monteiro ETB C. Acidity Theory of Atherosclerosis - History, Pathophysiology, Therapeutics and Risk Factors – A Mini Review. Positive Health Online, Edition 226, November 2015 at http://www.positivehealth.com/article/heart/acidity-theory-of-atherosclerosis-history-pathophysiology-therapeutics-and-risk-factors-a-mini-revie

34.   Monteiro ETB C. Stress as Cause of Atherosclerosis – The Acidity Theory pp.205-224 in Rosch PJ. Fat and Cholesterol Don’t Cause Heart Attacks and Statins Are Not The Solution 2016 Columbus Publishing, London at Amazon.com http://goo.gl/abyr4R

35.  Mencken H L. Exeunt Omnes. Smart Set, 60: 138–145: 1919

36.  Kraut JA, Coburn JW. Bone, Acid, and Osteoporosis, New England Journal of Medicine, 330;1821-1822: 1994 at https://www.nejm.org/doi/full/10.1056/NEJM199406233302510

37. Andrews J, Psaltis PJ et al. Coronary arterial calcification: A review of mechanisms, promoters and imaging. Trends Cardiovasc Med. 8(8):491-501: 2018 at DOI:10.1016/j.tcm.2018.04.007   https://www.ncbi.nlm.nih.gov/pubmed/29753636

38.  Goto K. Mineral metabolism in experimental acidosis. Journal of Biological Chemistry 36; 355-37:1918 at http://www.jbc.org/content/36/2/355.short  

39.  Arnett T. Regulation of bone cell function by acid-base balance. Proceedings of the Nutrition Society, 62, 511-520 2003 at https://www.ncbi.nlm.nih.gov/pubmed/14506899    / Arnett TR. Extracellular pH Regulates Bone Cell Function. The Journal of Nutrition, 138:415S-418S: 2008 at https://academic.oup.com/jn/article/138/2/415S/4665069

40.  Wachman A, Bernstein DS. Diet and osteoporosis. Lancet. 1968;1:958–9 at https://www.sciencedirect.com/science/article/pii/S0140673668909082

41.   Lynda Frassetto et al. Acid Balance, Dietary Acid Load, and Bone Effects—A Controversial Subject. Nutrients 2018, 10, 517 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946302/

42.  T Bjornheden, M Levin, M Evaldsson, O Wiklund. 1999. Evidence of hypoxic areas within the arterial wall in vivo, Arteriosclerosis, Thrombosis and Vascular Biology. 1999;19:870-876 at https://www.ahajournals.org/doi/full/10.1161/01.ATV.19.4.870

43.  Leake DS. 1997. Does an acidic pH explain why low-density lipoprotein is oxidized in atherosclerotic lesions? Atherosclerosis. 1997 Mar 21;129(2) at https://www.sciencedirect.com/science/article/pii/S0021915096060352

44.  Gown MA, Benditt PE. 1982. Lactate dehydrogenase (LDH) isozymes of human atherosclerotic plaques. Am J Pathol 1982, 107:316-321 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916248/

45.  G. Jackson, Lynne Atkinson, et al. Diagnosis of coronary artery disease by estimation of coronary sinus lactate. British Heart Journal. 1978, 40: 979-983 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC483520/

46.  Bemis CE, Gorlin R, et al. Progression of coronary artery disease: A clinical arteriographic study. Circulation, Vol XLVII, March 1973 at https://www.ahajournals.org/doi/pdf/10.1161/01.CIR.47.3.455

47.  Gertz EW, Wisneski JA, Neese R, Bristow JD, Searle GL, Hanlon JT: Myocardial lactate metabolism: evidence of lactate release during net chemical extraction in man. Circulation 1981, 63: 1273-1279 at https://www.ahajournals.org/doi/pdf/10.1161/01.CIR.63.6.1273

48.  Ghanshyam Palamaner Subash Shantha, Bruce Wasserman et al. Association of blood lactate with carotid atherosclerosis: The Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study. Atherosclerosis. 2013 May; 228(1): 249–255 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657708/

49.  Ross JM, Öberg J, Brené S, et al. High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio. Proc Natl Acad Sci U S A. 2010;107(46):20087-92 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993405/

50.  Yasunori Nagamine and Kenji Shima. Changes in Normal Reference Ranges for Serum Chemical Analyses with Ageing. Jpn J Geriat, 1989 26: 31-36 at https://www.ncbi.nlm.nih.gov/pubmed/2770027

51.  Sally Roberts, Pauline Colombier et al. Ageing in the musculoskeletal system - Cellular function and dysfunction throughout life. Acta Orthop. 2016 Dec; 87(Suppl 363): 15–25 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389428/

52.  Leopold JA. Vascular Calcification: An Age-Old Problem of Old Age. Circulation. 2013 June 18; 127(24): 2380–2382 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761061/

53. Rashdan NA and MacRae VE. P35 Calcification of murine aortic smooth muscle cells requires lactate production. Heart Volume, 2016; 102: Issue Suppl 8 at https://heart.bmj.com/content/102/Suppl_8/A13.1

54.  Crawford SO, Hoogeveen RC et al, Association of blood lactate with type 2 diabetes: The Atherosclerosis Risk in Communities Carotid MRI Study. International Journal of Epidemiology 2010 Dec; 39(6): 1647–1655 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992628/

55.  Juraschek SP, Shantha GPS et al. Lactate and Risk of Incident Diabetes in a Case-Cohort of the Atherosclerosis Risk in Communities (ARIC) Study. PLoS ONE , 2013 8(1): e55113 at https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0055113

56.  Janghorbani M, Van Dam RM et al . Systematic review of Type 1 and Type 2 diabetes mellitus and risk of fracture. Am. J. Epidemiol. 2007, 166(5), 495–505 at https://academic.oup.com/aje/article/166/5/495/87973

57.  Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with Type 1 and Type 2 diabetes – a meta-analysis. Osteoporos. Int. 2007, 18(4); 427–444 at https://link.springer.com/article/10.1007/s00198-006-0253-4

58.  Peter Jackuliak and Juraj Payer. Osteoporosis, Fractures, and Diabetes. Int J Endocrinol. 2014, Article ID 820615 at https://www.hindawi.com/journals/ije/2014/820615/

59.  John N. Stabley and Dwight A. Towler. Arterial Calcification In Diabetes: Preclinical Models And Translational Implications. Arterioscler Thromb Vasc Biol . February, 2017 37(2): 205–217 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480317/

60.  Juraschek SP, Julie K. Bower et al. Plasma Lactate and Incident Hypertension in the Atherosclerosis Risk in Communities Study. Am J Hypertens. 2015 Feb; 28(2): 216–224 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357800/

61.  Cappuccio FP et al. High blood pressure and bone-mineral loss in elderly white women: a prospective study. Study of Osteoporotic Fractures Research Group. Lancet.1999 Sep 18;354(9183):971-5 at https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)01437-3/fulltext

62.  Valenti V, Hartaigh B et al. Long-term Prognosis for Individuals with Hypertension Undergoing Coronary Artery Calcium Scoring. Int J Cardiol. 2015 May 6; 187: 534–540 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442064/

63.  Grossman C, Joseph Shemesh et al. Coronary Artery Calcification Is Associated With the Development of Hypertension. American Journal of Hypertension 2013, Volume 26, Issue 1, Pages 13–19 at https://academic.oup.com/ajh/article/26/1/13/164488

64.  Summers DN, Stephen Richmond et al. Cigarette smoke: Effects on lactate extraction in the presence of severe coronary atherosclerosis. American Heart Journal Volume 82, Issue 4, October 1971, Pages 458-467 at https://www.sciencedirect.com/science/article/pii/0002870371902304#!

65.  Yarlioglues M. Kaya MG et al. Dose-dependent acute effects of passive smoking on left ventricular cardiac function in health volunteers. J Investig Med, 2012; 60 (2): 517-22 at https://jamanetwork.com/journals/jama/fullarticle/194029

66.  AL-Bashaireh AM, Haddad LG et al. The Effect of Tobacco Smoking on Musculoskeletal Health: A Systematic Review. J Environ Public Health, 2018; 4184190 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077562/

67.  Lehmann N et al. Effect of smoking and other traditional risk factors on the onset of coronary artery calcification: results of the Heinz Nixdorf recall study. Atherosclerosis. 2014 Feb;232(2):339-45 at https://www.atherosclerosis-journal.com/article/S0021-9150(13)00703-X/abstract

68.  Bellomo R, Bench-to-bedside review: Lactate and the kidney. Crit Care. 2002; 6(4): 322–326 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC137458/

69.  D Yonova. Vascular calcification and metabolic acidosis in end stage renal disease. Hippokratia. 2009 Jul-Sep; 13(3): 139–140 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765290/

70.  Paul D Miller, Chronic kidney disease and osteoporosis: evaluation and management. Bonekey Rep. 2014; 3: 542 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078413/

71.  Nakamura S, Hatsue Ishibashi-Ueda et al. Coronary Calcification in Patients with Chronic Kidney Disease and Coronary Artery Disease. Clin J Am Soc Nephrol. 2009 Dec; 4(12): 1892–1900 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798876/

72.  Tomasz Stompór. Coronary artery calcification in chronic kidney disease: An update. World J Cardiol 2014 April 26; 6(4): 115-129 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999332/

73.  Marshall MW and Iacono JM. Changes in lactate dehydrogenase, LDH isoenzymes, lactate, and pyruvate as a result of feeding low fat diets to healthy men and women. Metabolism. 25: (2);169-78.1976 at https://www.sciencedirect.com/science/article/pii/0026049576900470

74.  Harold T. Edwards, Edward H. Bensley et al. Human Respiratory Quotients in Relation to Alveolar Carbon Dioxide and Blood Lactic Acid After Ingestion of Glucose, Fructose, or Galactose. Journal of Nutrition, 1944; 27: N 3: 241-251, at https://academic.oup.com/jn/article-abstract/27/3/241/4725717

75.  Hallfrisch J. Metabolic effects of dietary fructose. FASEB J, 1990 V 4; 2652-2660 at https://www.ncbi.nlm.nih.gov/pubmed/2189777

76.  James J. DiNicolantonio, Varshil Mehta et al. Not Salt But Sugar As Aetiological In Osteoporosis: A Review. Missouri Medicine May/June 2018, 115:3: 24 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140170/

77.  Sohyun Chun, Yuni Choi BS et al. Sugar-sweetened carbonated beverage consumption and coronary artery calcification in asymptomatic men and women. Am Heart J. 2016;177:17-2 at https://www.sciencedirect.com/science/article/pii/S0002870316300230

78.  Tian Hu, Jacobs DR et al. Low-carbohydrate diets and prevalence, incidence and progression of coronary artery calcium in the Multi-Ethnic Study of Atherosclerosis (MESA). British Journal of Nutrition, Published online: 11 January 2019 at https://www.ncbi.nlm.nih.gov/pubmed/30630542

79.  Chang X. and Wei C. Glycolysis and rheumatoid arthritis. International Journal of Rheumatic Diseases, 2011; 14 at https://onlinelibrary.wiley.com/doi/full/10.1111/j.1756-185X.2011.01598.x

80.  El-Gabalawy HD and Lipsky PE. Why do we not have a cure for rheumatoid arthritis? Arthritis Res 2002, 4 (suppl 3):S297-S30 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240144/

81.  Karmakar S, Kay J et al. Bone Damage in Rheumatoid Arthritis – Mechanistic Insights and Approaches to Prevention Rheum Dis Clin North Am. 2010 May; 36(2): 385–404 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905601/

82.  Giles JT, Szklo M et al. Coronary arterial calcification in rheumatoid arthritis: comparison with the Multi-Ethnic Study of Atherosclerosis. Arthritis Research & therapy. 2009; 11(2) at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688181/

83.  Yiu KH, Mok MY et al. Prognostic role of coronary calcification in patients with rheumatoid arthritis and systemic lupus erythematosus. Clinical and Experimental Rheumatology. 2012; 30(3):345–50 at https://www.ncbi.nlm.nih.gov/pubmed/22409930

84.  Mehdi Kargarfard, Parinaz Poursafa et al. Effects of Exercise in Polluted Air on the Aerobic Power, Serum Lactate Level and Cell Blood Count of Active Individuals. Int J Prev Med. 2011 Jul-Sep; 2(3): 145–150 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143527/

85.  Vu H. Nguyen. Environmental Air Pollution and the Risk of Osteoporosis and Bone Fractures. J Prev Med Public Health. 2018 Jul; 51(4): 215–216 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078918/

86.  Kaufman JD, Adar SD et al. Association between air pollution and coronary artery calcification within six metropolitan areas in the USA (the Multi-Ethnic Study of Atherosclerosis and Air Pollution: a longitudinal cohort study. The Lancet Volume 388, Issue 10045, 13–19 August 2016, Pages 696-704 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019949/

87.  Kazuo Sakaguchi, Keiko Iizuka et al. Factors Influencing Warfarin Requirements – Warfarin Increases Lactate Dehydrogenase Concentration in Patients with Valve Prostheses. Jpn. J. Pharm. Health Care Sci, 2004, 30; No. 9 at https://www.jstage.jst.go.jp/article/jjphcs2001/30/9/30_9_614/_article

88.  Rezaieyazdi Z, Falsoleiman H et al. Reduced bone density in patients on long-term warfarin. Int J Rheum Dis. 2009 Jul;12(2):130-5 at https://www.ncbi.nlm.nih.gov/pubmed/20374330

89.  Han KH, O'Neill WC. Increased Peripheral Arterial Calcification in Patients Receiving Warfarin. J Am Heart Assoc. 2016;5(1) at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859382/

90.  Tantisattamo E, Han KH, O'Neill WC. Increased vascular calcification in patients receiving warfarin. Arterioscler Thromb Vasc Biol. 2015;35(1):237-42 at https://www.ahajournals.org/doi/10.1161/ATVBAHA.114.304392

91.  Ralph DeFronzo, Fleming GA et al. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism V. 65, Issue 2, February 2016, Pages 20-29 at https://www.ncbi.nlm.nih.gov/pubmed/26773926

92.  Lalau JD. Lactic acidosis induced by metformin: incidence, management and prevention. Saf. 2010 Sep 1;33(9):727-40 at https://www.ncbi.nlm.nih.gov/pubmed/20701406

93.  Emma Fitzgerald, Stephen Mathieu and Andrew Ball. Metformin associated lactic acidosis. BMJ 2009; 339 at https://www.bmj.com/content/339/bmj.b3660

94.  Sahar Kamal Hegaz. Evaluation of the anti-osteoporotic effects of metformin and sitagliptin in postmenopausal diabetic women. J Bone Miner Metab 2015 Mar;33(2):207-12 at https://www.ncbi.nlm.nih.gov/pubmed/24633493

95.  Goldberg RB, Aroda VR et al. Effect of long-term metformin and lifestyle in the diabetes prevention program and its outcome study on coronary artery calcium. Circulation 2017 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526695/

96.  De Pinieux G, P. Chariot et al. Lipid-lowering drugs and mitochondrial function: effects of HMGCoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio. Br J Clin Pharmacol. 1996 Sep;42(3):333-7 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042680/

97.  Dhiaa A. Taha, Cornelia H. De Moor et al. The role of acid-base imbalance in statin-induced myotoxicity. Transl Res. 2016 Aug; 174: 140–160.e14 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967449/

98.  Beatrice A. Golomb and Marcella A. Evans, Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism. Am J Cardiovasc Drugs. 2008; 8(6): 373–418 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849981/

99.  Jessica M. Peña, Sara Aspberg et al. Statin Therapy and Risk of Fracture Results from the JUPITER Randomized Clinical Trial. JAMA Intern Med.2015;175(2):171-177 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578729/

100. Iryna Dykun, Nils Lehmann et al. Statin Medication Enhances Progression of Coronary Artery Calcification – The Heinz Nixdorf Recall Study JACC Vol, 68 NO. 19, 2016; Pages 2123-2125 at http://www.onlinejacc.org/content/accj/68/19/2123.full.pdf

101. Morgan J, Leake DS. 1995. Oxidation of low density lipoprotein by iron or copper at acidic pH. J Lipid Res. Dec;36(12):2504-12 at http://www.jlr.org/content/36/12/2504.full.pdf

102. Patterson RA, Leake DS. 1998. Human serum, cysteine and histidine inhibit the oxidation of low density lipoprotein less at acidic pH. FEBS Lett. Sep 4;434(3):317- 21 at https://www.ncbi.nlm.nih.gov/pubmed/9742946

103. Wen Y, Leake DS. 2007. Low density Lipoprotein oxidation undergoes within lysosome in cells. Circ.Res. 100;1337-1343 at https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.107.151704

104. Viet T. Le, Stacey Night et al. Coronary Artery Calcium is Associated with 90-Day MACE at Any Level of Ischemic Burden in Patients Referred for PET/CT. JACC, Volume 73: Issue 9: March 12, 2019 at http://www.onlinejacc.org/content/73/9_Supplement_1/1480

105. Monteiro ETB C. Stress as Cause of Heart Attacks - The Myogenic Theory originally published in the Wise Traditions Journal (Fall edition, 2014) from Weston A. Price Foundation. Reproduced in Positive Health Online (Issue 222, May 2015), at www.positivehealth.com/article/heart/stress-ascause-of-heart-attacks-the-myogenic-theory

106. Monteiro ETB C. ‘Intense Stress Leading to Raised Production and Accumulation of Lactate in Brain Ischemia – The Ultimate Cause of Acute Stroke: Mechanism, Risk Factors and Therapeutics.’ published in Positive Health Online, Edition 247, July 2018 at http://www.positivehealth.com/article/heart/intense-stress-leading-to-accumulation-of-lactate-in-brain-ischemia

107. Hermann DM, Gronewold J, et al. on behalf of the Heinz Nixdorf Recall Study Investigative Group. Coronary Artery Calcification is an Independent Stroke Predictor in the General Population. Stroke. 2013;44:1008-1013 at https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.111.678078

108. Chaikriangkrai K, Jhun HY et al. Coronary artery calcium score as a predictor for incident stroke: Systematic review and meta-analysis. Int J Cardiol. 2017 Jun 1;236:473-477 at https://www.ncbi.nlm.nih.gov/pubmed/28202259

109. Monteiro ETB C, “Stress as the Inductive Factor for Increased Lactate Production: The Evolutionary Path to Carcinogenesis”. Positive Health Online, Edition 241, October, 2017 at http://www.positivehealth.com/article/cancer/stress-inductive-factor-for-increased-lactateproduction-evolutionary-path-to-carcinogenesis

110. Whitlock MC et al. Cancer and Its Association with the Development of Coronary Artery Calcification: An Assessment from the Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc. 2015;4:e002533 at http://jaha.ahajournals.org/content/4/11/e002533.full

111. Ahmed El-Sabbagh, Medhat M Osman et al, Chemotherapy-induced coronary arteries calcium score deterioration as detected with unenhanced CT portion of FDG PET/CT. Am J Nucl Med Mol Imaging 2018;8(5):303-310 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261876/

112. Marina V. Shirmanova, Irina N. Druzhkova et al. Chemotherapy with cisplatin: insights into intracellular pH and metabolic landscape of cancer cells in vitro and in vivo. Sci Rep. 2017 Aug 21;7(1):8911 at https://www.ncbi.nlm.nih.gov/pubmed/28827680

113. Henein M, Granasen G, Schmermund A. High dose and long-term statin therapy accelerate coronary artery calcification. Int J Cardiol. 2015 Apr 1;184:581-6 at https://www.internationaljournalofcardiology.com/article/S0167-5273(15)00199-0/fulltext

114. Takata K, Imaizumi S, Zhang B. Stabilization of high-risk plaques. Cardiovasc Diagn Ther. 2016 Aug; 6(4): 304–321. https://doi.org/10.21037/cdt.2015.10.03

115. Rogers MA and Aikawa E. Cardiovascular calcification: Artificial intelligence and big data accelerate mechanistic discovery. Nature Reviews Cardiology, volume 16, pages 261–274; 2019 at https://www.nature.com/articles/s41569-018-0123-8

116. Armin Arbab-Zadeh, Valentin Fuster. "The Myth of the “Vulnerable Plaque -- Transitioning from a Focus on Individual Lesions to Atherosclerotic Disease Burden for Coronary Artery Disease Risk Assessment", J Am Coll Cardiol. 2015 at http://content.onlinejacc.org/article.aspx?articleID=2091922

117. Leutner M, Matzhold C et al. Diagnosis of osteoporosis in statin-treated patients is dose-dependent. Ann Rheum Dis. 2019 at https://ard.bmj.com/content/early/2019/09/25/annrheumdis-2019-215714

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About Carlos ETB Monteiro

Carlos ETB Monteiro is an independent researcher and scientist from Brazil with 43 years’ experience in dealing with medical matters. In 1972 he became a follower in the scientific plan from Dr Quintiliano H de Mesquita, originator of the myogenic theory of myocardial infarction and other pioneer medical contributions (QHM Memorial). In 1999 he participated in the foundation of Infarct Combat Project and elected president by the board of directors. Carlos Monteiro is still supporting Dr Mesquita’s medical and scientific ideas, through Infarct Combat Project. Recently he has developed a new hypothesis to explain atherosclerosis that was named acidity theory of atherosclerosis. The blog new evidences about his Acidity Theory you can find here.

He is a non-official member of "The International Network of Cholesterol Skeptics (THINCS -  www.thincs.org) and Fellow of the American Institute of Stress (www.stress.org) and is also a  member of the honorary board of Weston A Price Foundation (www.westonaprice.org/). His recent book Acidity Theory of Atherosclerosis - New Evidences, 2012 is available for Kindle readers and in paperback at www.Amazon.com  also in paperback. Carlos Monteiro is one of the signatories of a letter to The Academy Obesity Steering Group entitled “Obesity is an Iatrogenic Disease”. He recently presented two lectures in  the Fourth International Conference of Advanced Cardiac Sciences - The King of Organs Conference, 2012, Saudi Arabia: the first about the Myogenic Theory of Myocardial Infarction (Powerpoint presentation and video),  the second about the Acidity Theory of Atherosclerosis (Powerpoint presentation and video). Carlos Monteiro may be contacted via secretary@infarctcombat.org   www.infarctcombat.org/

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