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The The Acidity Acidity Theory Theory of of

Atherosclerosis Atherosclerosis

Fourth International Conference on
Advanced Cardiac Sciences
King King of of Organs Organs, 2012 , 2012
Kingdom Kingdom of of Saudi Saudi Arabia Arabia

Carlos Monteiro Carlos Monteiro
Infarct Infarct Combat Combat Project Project
http://infarctcombat.org http://infarctcombat.org

In July 29, 2006, during a discussion in the internal forum at internet of In July 29, 2006, during a discussion in the internal forum at internet of
the International Network of Cholesterol Skeptics (THINCS) , about the the International Network of Cholesterol Skeptics (THINCS) , about the
role of mechanical forces in atherosclerosis, Melchior Meijer, a journalist role of mechanical forces in atherosclerosis, Melchior Meijer, a journalist
specialized in medical area, noticed about the demonstration by scientists specialized in medical area, noticed about the demonstration by scientists
from California that normal stretching/relaxing of an artery does not from California that normal stretching/relaxing of an artery does not
produce atherosclerosis, while stretching/relaxing in different directions produce atherosclerosis, while stretching/relaxing in different directions
simultaneously on every heart beat does. simultaneously on every heart beat does.
Dr. Paul Dr. Paul Rosch Rosch, participating in the discussion about these findings, told , participating in the discussion about these findings, told
that in relation of the contribution of psychological stress his friend that in relation of the contribution of psychological stress his friend
Meyer Meyer Texon Texon, the , the developer of the hemodynamic theory of developer of the hemodynamic theory of
atherosclerosis, atherosclerosis, conceded conceded to him in to him in a a conversation that stress might conversation that stress might
accelerate the development of atherosclerotic lesions by aggravating the accelerate the development of atherosclerotic lesions by aggravating the
basic mechanism basic mechanism of shear stress, that of shear stress, that he felt was responsible. he felt was responsible.
Few Few days after, inspired by days after, inspired by the findings from the researchers in California the findings from the researchers in California
and by the and by the information brought by information brought by Dr. Paul Dr. Paul Rosch Rosch, , I I came to came to the draft the draft
about the acidity theory of atherosclerosis about the acidity theory of atherosclerosis..



Gaskett Gaskett demonstrated in 1880 that acid solutions have demonstrated in 1880 that acid solutions have effects on effects on the the
contractility of heart tissues and vascular smooth muscle, contractility of heart tissues and vascular smooth muscle, reasoning that reasoning that
this was one important mechanism for the local this was one important mechanism for the local regulation of regulation of blood flow blood flow
during increased metabolic during increased metabolic activity. activity.

(Gaskell (Gaskell WH. On the tonicity of the heart and blood vessels. J WH. On the tonicity of the heart and blood vessels. J Physiol Physiol 1880;3:48 1880;3:48--75) 75)

Zsoter Zsoter et al have shown in 1961 that reduction of blood pH increases blood et al have shown in 1961 that reduction of blood pH increases blood
flow. flow.

((Zsoter Zsoter, , Bandeman Bandeman L, L, Chappel Chappel CL. The effect of local pH changes on blood flow in CL. The effect of local pH changes on blood flow in
the dog. Am Heart J. 1961;61: 777 the dog. Am Heart J. 1961;61: 777--782) 782)



In 1977 James In 1977 James P. Henry and Patricia M. Stephens were the first to P. Henry and Patricia M. Stephens were the first to
postulate postulate that chronic stress or the constantly heightened sympathetic that chronic stress or the constantly heightened sympathetic--
adrenomedullary adrenomedullary activity may lead to activity may lead to atherosclerosis atherosclerosis and and cardiovascular cardiovascular
disease*. disease*.


*J.P *J.P. Henry , P.M. Stephens. Stress, Health, and the Social Environment: A . Henry , P.M. Stephens. Stress, Health, and the Social Environment: A
Sociobiologic Sociobiologic Approach to Medicine. Springer; First edition, Dec 21 Approach to Medicine. Springer; First edition, Dec 21 1977 1977
Sequence Sequence of of events* events*

I. Sympathetic dominance by continuous stress plus I. Sympathetic dominance by continuous stress plus
II. Deficiency in production of endogenous digitalis II. Deficiency in production of endogenous digitalis--like like compounds compounds with with
alterations of alterations of sodium sodium--potassium pump potassium pump activity results in activity results in
III. Lowered pH (acidity) that increases perfusion pressure and provokes III. Lowered pH (acidity) that increases perfusion pressure and provokes
effects on contractility of coronary arteries, leading to changes in effects on contractility of coronary arteries, leading to changes in
hemodynamic shear stress and atherosclerosis as hemodynamic shear stress and atherosclerosis as consequence. consequence.

*Carlos *Carlos ETB ETB Monteiro Monteiro, Acidic environment evoked by chronic stress: A novel , Acidic environment evoked by chronic stress: A novel
mechanism to explain mechanism to explain atherogenesis atherogenesis. Available from Infarct Combat Project, . Available from Infarct Combat Project,
January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf



The The heart is an organ of high metabolic activity heart is an organ of high metabolic activity that cannot rest as other that cannot rest as other
body muscles, being susceptible to drops in pH during ischemia and body muscles, being susceptible to drops in pH during ischemia and
hypoxia. hypoxia. The chronic or acute elevated catecholamine release, mainly The chronic or acute elevated catecholamine release, mainly
from sympathetic nerve terminals in cardiac from sympathetic nerve terminals in cardiac tissue, may tissue, may accelerate the accelerate the
myocardial myocardial glycolysis glycolysis leading to significant increase in lactate production leading to significant increase in lactate production..
The The association of increased lipid levels with abnormal lactate association of increased lipid levels with abnormal lactate
metabolism may provide a useful screening test for the detection of metabolism may provide a useful screening test for the detection of
coronary artery coronary artery disease, according a study. Other study has demonstrated disease, according a study. Other study has demonstrated
that that plasma lipid abnormalities and myocardial lactate production plasma lipid abnormalities and myocardial lactate production were were
significantly associated with subsequent significantly associated with subsequent arteriographic arteriographic progression. The progression. The
amount of lactate released by the myocardium has been shown to be amount of lactate released by the myocardium has been shown to be
related to the severity of coronary artery disease. related to the severity of coronary artery disease.
In In our opinion the raise in plasma lipids presented in these studies might our opinion the raise in plasma lipids presented in these studies might
be a response to injury of the arterial endothelium due to an increased be a response to injury of the arterial endothelium due to an increased
release of release of lactate and the resulting changes in hemodynamic shear stress. lactate and the resulting changes in hemodynamic shear stress.
The response to injury concept is supported by the acidity theory of The response to injury concept is supported by the acidity theory of
atherosclerosis. atherosclerosis.


(G (G. Jackson, . Jackson, et al. et al. Diagnosis of coronary artery disease by estimation of coronary Diagnosis of coronary artery disease by estimation of coronary
sinus lactate. British Heart Journal, 1978, 40, 979 sinus lactate. British Heart Journal, 1978, 40, 979--983 983 ; Bemis ; Bemis CE, CE, Gorlin Gorlin R, et al. R, et al.
Progression of coronary artery disease: A clinical Progression of coronary artery disease: A clinical arteriographic arteriographic study. Circulation, study. Circulation,
Vol Vol XLVII, March XLVII, March 1973) 1973)

TThe sympathetic activation with elevation of circulating catecholamine he sympathetic activation with elevation of circulating catecholamine
((adrenaline adrenaline, etc..), cause , etc..), cause coronary coronary vasoconstriction vasoconstriction and and consequent consequent
reduction reduction in in blood blood flow flow..
On the other hand the increased lactate (or decreased blood pH) may evoke On the other hand the increased lactate (or decreased blood pH) may evoke
vascular smooth muscle relaxation and increase of blood vascular smooth muscle relaxation and increase of blood flow flow..
These opposite forces working in sequence These opposite forces working in sequence -- with the sympathetic overdrive with the sympathetic overdrive
leading to metabolic acidosis, in our view, may be reconciled to partially leading to metabolic acidosis, in our view, may be reconciled to partially
explain the occurrence of the resulting abnormal stretching/relaxing of explain the occurrence of the resulting abnormal stretching/relaxing of
coronary arteries, in different directions, simultaneously, producing changes coronary arteries, in different directions, simultaneously, producing changes
in hemodynamic shear stress leading to atherosclerosis. in hemodynamic shear stress leading to atherosclerosis.


Book Acidity Theory of Atherosclerosis Book Acidity Theory of Atherosclerosis New Evidences, 2012 New Evidences, 2012

Studies suggest that some risk factors for coronary artery disease, like Studies suggest that some risk factors for coronary artery disease, like
stress (anxiety, hostility, stress (anxiety, hostility, extreme physical exertion extreme physical exertion , etc..), high , etc..), high
carbohydrate diets and carbohydrate diets and smoke may raise smoke may raise total cholesterol and low density total cholesterol and low density
lipoproteins lipoproteins levels. levels.
Also, it is interesting to notice that in stress conditions, high carbohydrate Also, it is interesting to notice that in stress conditions, high carbohydrate
diets and cigarette smoking there is a significant elevation in blood diets and cigarette smoking there is a significant elevation in blood
lactate levels. lactate levels.

As Dr. Malcolm Kendrick use to say: As Dr. Malcolm Kendrick use to say:
"Do cigarettes contain fat? No, not at all. So, how can smoking a cigarette, "Do cigarettes contain fat? No, not at all. So, how can smoking a cigarette,
containing no fat or cholesterol, end up depositing fat and cholesterol in the containing no fat or cholesterol, end up depositing fat and cholesterol in the
artery walls. What is the mechanism for that? artery walls. What is the mechanism for that?


References at the book: Acidity Theory of atherosclerosis References at the book: Acidity Theory of atherosclerosis New Evidences, 2012 New Evidences, 2012
In the next slides we will discuss about the In the next slides we will discuss about the
dysregulation dysregulation of the autonomic nervous system, as the of the autonomic nervous system, as the
underlying mechanism in psychosocial and other risk underlying mechanism in psychosocial and other risk
factors for atherosclerosis/coronary artery disease that factors for atherosclerosis/coronary artery disease that
are related with sympathetic dominance, through are related with sympathetic dominance, through
sympathetic over sympathetic over--activity or parasympathetic activity or parasympathetic
withdrawal. withdrawal.



The The 5 specific psychosocial domains 5 specific psychosocial domains that contribute that contribute significantly to the significantly to the
pathogenesis and expression of coronary artery pathogenesis and expression of coronary artery disease are: disease are:
Depression; Depression;
Anxiety; Anxiety;
Personality Personality factors and character factors and character traits; traits;
Social isolation Social isolation;;
Chronic Chronic life stress. life stress.


(Alan (Alan Rozanski Rozanski, James A. Blumenthal and Jay Kaplan. Impact of Psychological , James A. Blumenthal and Jay Kaplan. Impact of Psychological
Factors on the Pathogenesis of Cardiovascular Disease and Implications for Factors on the Pathogenesis of Cardiovascular Disease and Implications for
Therapy. Circulation. 1999;99:2192 Therapy. Circulation. 1999;99:2192--2217; 2217; Veith Veith RC et al. Sympathetic RC et al. Sympathetic nervous nervous
system activity in major depression. Basal and system activity in major depression. Basal and desipramine desipramine--induced alterations in induced alterations in
plasma norepinephrine kinetics. plasma norepinephrine kinetics. Arch Arch Gen Psychiatry. 1994 May;51(5): Gen Psychiatry. 1994 May;51(5):411 411--22) 22)


Atherosclerosis Atherosclerosis and age are intimately linked, being the best example of an and age are intimately linked, being the best example of an
age age--related disease. related disease. It It is is generally generally accepted accepted that sympathetic nervous activity that sympathetic nervous activity
increases progressively with age. Also that plasma noradrenaline levels increases progressively with age. Also that plasma noradrenaline levels
increase may be mediated by the age related impairment of increase may be mediated by the age related impairment of baroreflex baroreflex
sensitivity sensitivity..



(Ziegler MG, Lake CR and (Ziegler MG, Lake CR and Kopin Kopin IJ. Plasma noradrenaline increases with age. Nature IJ. Plasma noradrenaline increases with age. Nature
261, 33 261, 33 --335 (27 May 1976); Shimada and all. Age 335 (27 May 1976); Shimada and all. Age--related changes of related changes of baroreflex baroreflex function, function,
plasma norepinephrine , and blood pressure. Hypertension 7:113 plasma norepinephrine , and blood pressure. Hypertension 7:113--117, 1985; 117, 1985; Narkiewicz Narkiewicz
et al. Gender et al. Gender--selective interaction between aging, blood pressure and sympathetic selective interaction between aging, blood pressure and sympathetic
nerve activity. Hypertension 2005;45:522 nerve activity. Hypertension 2005;45:522--525) 525)


A A recent study have demonstrated that sympathetic predominance may recent study have demonstrated that sympathetic predominance may
favor the development of sustained hypertension and favor the development of sustained hypertension and
hypercholesterolemia early in life, and lead to increased susceptibility to hypercholesterolemia early in life, and lead to increased susceptibility to
vascular complications. vascular complications.



((Palatini Palatini PP, et al. , et al. Evolution Evolution of of blood blood pressure pressure and and cholesterol cholesterol in in stage stage 1 1
hypertension hypertension: role : role of of autonomic autonomic nervous nervous system system activity activity. . Journal Journal of of
Hypertension Hypertension 2006, 2006, 24:1375 24:1375--1381) 1381)


Hypertension Hypertension is considered as an important risk factor for the is considered as an important risk factor for the
development of atherosclerosis, with these processes sharing some development of atherosclerosis, with these processes sharing some
common mechanisms. The endothelium is usually placed as the probable common mechanisms. The endothelium is usually placed as the probable
central focus for the effects in both diseases, with evidences leading to the central focus for the effects in both diseases, with evidences leading to the
postulation that hypertension predispose and accelerate atherosclerosis. postulation that hypertension predispose and accelerate atherosclerosis.
The sympathetic activation plays an important role in the regulation of The sympathetic activation plays an important role in the regulation of
the blood the blood pressure. pressure.



((Grassi Grassi G, G, Seravalle Seravalle G et al. Sympathetic and G et al. Sympathetic and baroreflex baroreflex cardiovascular control in cardiovascular control in
hypertension hypertension--related left ventricular dysfunction. Hypertension related left ventricular dysfunction. Hypertension 2009;53:205 2009;53:205--209 ; 209 ;
Grassi Grassi G, G, Bertoli Bertoli S, S, Seravalle Seravalle G. Sympathetic nervous system: role in hypertension G. Sympathetic nervous system: role in hypertension
and in chronic kidney disease. and in chronic kidney disease. Curr Curr Opin Opin Nephrol Nephrol Hypertens Hypertens, 2010, Nov , 2010, Nov 10; Joyner 10; Joyner
MJ, MJ, Charkoudian Charkoudian N and N and Wallin Wallin BG. Sympathetic nervous system and blood BG. Sympathetic nervous system and blood
pressure in humans. Individualized patterns of regulation and their implications. pressure in humans. Individualized patterns of regulation and their implications.
Hypertension 2010; Hypertension 2010; 56:10 56:10--16) 16)



Patients Patients with chronic kidney disease are at increased risk of with chronic kidney disease are at increased risk of
atherosclerotic cardiovascular disease. atherosclerotic cardiovascular disease.
A marked increase in sympathetic neural discharge, as assessed via the A marked increase in sympathetic neural discharge, as assessed via the
microneurographic microneurographic technique, has been shown to occur in the technique, has been shown to occur in the predialytic predialytic
stage of chronic renal failure. Recent evidence, however, indicates that stage of chronic renal failure. Recent evidence, however, indicates that
also in the earlier clinical phases of kidney disease, sympathetic activation also in the earlier clinical phases of kidney disease, sympathetic activation
is detectable. Further data show that sympathetic neural mechanisms is detectable. Further data show that sympathetic neural mechanisms
participate in renal and/or hypertensive disease progression, participate in renal and/or hypertensive disease progression, favoring favoring the the
development of target organ damage. development of target organ damage.

((Grassi Grassi G, G, Bertolli Bertolli S, S, Seravalle Seravalle G. Sympathetic nervous system: role in hypertension G. Sympathetic nervous system: role in hypertension
and in chronic kidney disease. and in chronic kidney disease. Curr Curr Opin Opin Nephrol Nephrol Hypertens Hypertens 2012 Jan;21(1):46 2012 Jan;21(1):46--51 51.) .)


Patients Patients with diabetes are at increased risk for with diabetes are at increased risk for atherosclerosis. atherosclerosis. It has long It has long
been recognized that cardiac autonomic neuropathy increases morbidity been recognized that cardiac autonomic neuropathy increases morbidity
and mortality in diabetes and may have greater predictive power than and mortality in diabetes and may have greater predictive power than
traditional risk factors for cardiovascular events. Significant morbidity traditional risk factors for cardiovascular events. Significant morbidity
and mortality and mortality in diabetes can in diabetes can now be attributable to autonomic imbalance now be attributable to autonomic imbalance
between the sympathetic and parasympathetic nervous system regulation between the sympathetic and parasympathetic nervous system regulation
of of cardiovascular function. cardiovascular function.

(Beckman (Beckman JA,Creager JA,Creager MA, Libby P. Diabetes and Atherosclerosis. JAMA. 2002; MA, Libby P. Diabetes and Atherosclerosis. JAMA. 2002;
287(19): 287(19):2570 2570--2581; 2581; Vinik Vinik AI, AI, Zieglert Zieglert D. Autonomic imbalance: prophet of doom or D. Autonomic imbalance: prophet of doom or
scope for hope? scope for hope? Diabet Diabet. Med. 28, 643 . Med. 28, 643--651 (2011) 651 (2011)

Cigarette Cigarette smoking increases efferent sympathetic nerve traffic acutely, as smoking increases efferent sympathetic nerve traffic acutely, as
well norepinephrine and epinephrine release well norepinephrine and epinephrine release. . The acute The acute
sympathoexcitatory sympathoexcitatory effects of smoking on the cardiovascular system are effects of smoking on the cardiovascular system are
partially mediated by catecholamine release, muscle sympathetic nerve partially mediated by catecholamine release, muscle sympathetic nerve
excitation and peripheral chemoreceptor sensitivity increase, consecutive excitation and peripheral chemoreceptor sensitivity increase, consecutive
to nicotinic receptor stimulation in the autonomic nervous to nicotinic receptor stimulation in the autonomic nervous system. Both system. Both
active smoking and exposure to active smoking and exposure to environmental environmental tobacco smoke are tobacco smoke are
associated with the progression of atherosclerosis as indexed by intimal associated with the progression of atherosclerosis as indexed by intimal--
medial thickness of the carotid artery assessed by medial thickness of the carotid artery assessed by ultrasound ultrasound. Carotid . Carotid
intima intima--media media thickness is thickness is a valid surrogate measure for coronary a valid surrogate measure for coronary
atherosclerosis. atherosclerosis.

Blood lactate levels are increased after passive smoking. Blood lactate levels are increased after passive smoking.

((Niedermaier Niedermaier ON, Smith ML. ON, Smith ML. Influence of cigarette smoking on human autonomic Influence of cigarette smoking on human autonomic
function. Circulation 1993, 88:562 function. Circulation 1993, 88:562--571 571 ; ; Adamopoulus Adamopoulus D, van de Borne P and D, van de Borne P and
Argacha Argacha JF, New insights into the sympathetic, endothelial and coronary effects of JF, New insights into the sympathetic, endothelial and coronary effects of
nicotine. nicotine. Clin Clin Exp Exp Pharmacol Pharmacol Physiol Physiol 2008; 35(4): 2008; 35(4): 458 458--63; Howard 63; Howard G et al, Cigarette G et al, Cigarette
smoking and progression of atherosclerosis: The Atherosclerosis Risk in smoking and progression of atherosclerosis: The Atherosclerosis Risk in
Communities (ARIC) Study. JAMA, 1998 Jan 14;279(2):119 Communities (ARIC) Study. JAMA, 1998 Jan 14;279(2):119--24. 24. Yarlioglues Yarlioglues M. M. Kaya Kaya
MG et al. Dose MG et al. Dose--dependent acute effects of passive smoking on left ventricular dependent acute effects of passive smoking on left ventricular
cardiac function in health volunteers. J cardiac function in health volunteers. J Investig Investig Med 2012 , Feb; 60 (2): 517 Med 2012 , Feb; 60 (2): 517--22) 22)


A A recent recent study study in in humans humans have have confirmed confirmed the the association association of of the the exposure exposure
to to ambient ambient air air pollution pollution and and atherosclerosis atherosclerosis, , through through the the progression progression of of
carotid carotid artery artery intima intima--media media thickness thickness . . Also Also, some , some investigators investigators have have
demonstrated demonstrated that that particulate particulate air air pollutants pollutants continuous continuous exposition exposition
decreases decreases the the heart heart rate rate variability variability and and may lead to may lead to an an impaired impaired
autonomic autonomic control control with with potential potential acceleration acceleration in in the the progression progression of of
atherosclerosis atherosclerosis..







(Nino (Nino Kunzli Kunzli et al. et al. ""Ambient Ambient Air Air Pollution Pollution and and the the Progression Progression of of Atherosclerosis Atherosclerosis
in in Adults Adults." ." PloS PloS ONE 5(2): ONE 5(2): e9096, e9096, February February 8, 8, 2010; 2010; Duanping Duanping Liao Liao et al. et al.
Association Association of of Higher Higher Levels Levels of of Ambient Ambient Criteria Criteria Pollutants Pollutants with with Impaired Impaired Cardiac Cardiac
Autonomic Autonomic Control Control: A : A Population Population--based based Study Study, , Am Am J J Epidemiol Epidemiol 2004;159:768 2004;159:768777; 777;
C. C. Arden Arden Pope Pope III et al. III et al. Ambient Ambient Particulate Particulate Air Air Pollution Pollution, Heart Rate , Heart Rate Variability Variability, ,
and and Blood Blood Markers Markers of of Inflammation Inflammation in a in a Panel Panel of of Elderly Elderly Subjects Subjects. Environmental . Environmental
Health Perspectives, V 112; N 3: Health Perspectives, V 112; N 3: March March 2004; 2004; Heikki Heikki V et al. V et al. Heart Rate Heart Rate Variability Variability
and and Progression Progression of of Coronary Coronary Atherosclerosis Atherosclerosis. . Arteriosclerosis Arteriosclerosis, , Thrombosis Thrombosis, , and and
Vascular Vascular Biology Biology. . 1999;19:1979 1999;19:1979--1985) 1985)

Road traffic and aircraft noise near airports causes stress reactions similar Road traffic and aircraft noise near airports causes stress reactions similar
to other stressors in the occupational and ambient environment. In these to other stressors in the occupational and ambient environment. In these
situations of sympathetic and endocrine arousal, concentrations of stress situations of sympathetic and endocrine arousal, concentrations of stress
hormones in the blood are increased. Laboratory and epidemiological hormones in the blood are increased. Laboratory and epidemiological
studies have demonstrated a link between noise and cardiovascular studies have demonstrated a link between noise and cardiovascular
disease. disease.

((Babisch Babisch W. Stress hormones in the research on cardiovascular effects of noise. W. Stress hormones in the research on cardiovascular effects of noise.
Noise Health 2003;5:1 Noise Health 2003;5:1--11; 11; Babisch Babisch W. Transportation noise and cardiovascular W. Transportation noise and cardiovascular
risk: updated review and synthesis of epidemiological studies indicate that the risk: updated review and synthesis of epidemiological studies indicate that the
evidence has increased. Noise Health 2006;8:1 evidence has increased. Noise Health 2006;8:129; Eriksson C, 29; Eriksson C, Rosenlund Rosenlund M, M,
Pershagen Pershagen G, G, Hilding Hilding A, A, Ostenson Ostenson C, C, Bluhm Bluhm G. Aircraft noise and incidence of G. Aircraft noise and incidence of
hypertension. Epidemiology 2007;18:716 hypertension. Epidemiology 2007;18:716721; 721; Jarup Jarup L, L, Babisch Babisch W, W, Houthuijs Houthuijs D, D,
Pershagen Pershagen G, G, Katsouyanni Katsouyanni K, K, Cadum Cadum E, Dudley M, E, Dudley M, Savigny Savigny P, P, Seiffert Seiffert I, Swart W, I, Swart W,
et al. et al. Hypertension and exposure to noise near airports: the HYENA Study. Hypertension and exposure to noise near airports: the HYENA Study.
Environ Health Environ Health Perspect Perspect 2008;116:329 2008;116:329333) 333)


It It is well established that the is well established that the sympathetic nervous system sympathetic nervous system activity is also activity is also
influenced by food ingestion, and that diet composition plays an influenced by food ingestion, and that diet composition plays an
important role. important role. High High carbohydrate diets, particularly in the form of high carbohydrate diets, particularly in the form of high--
glycemic glycemic carbohydrate carbohydrate, have the ability to directly induce endothelial , have the ability to directly induce endothelial
dysfunction, vascular inflammation and subsequent development of dysfunction, vascular inflammation and subsequent development of
atherosclerosis. atherosclerosis. A study from 2009 defends A study from 2009 defends that the that the widespread use of widespread use of
starchy food and sugars has brought about a new metabolic problem: a starchy food and sugars has brought about a new metabolic problem: a
chronically chronically increased increased sympathetic nervous system activity, sympathetic nervous system activity, where the where the
high high--glycemic index nutrition has been suggested to play a key role in the glycemic index nutrition has been suggested to play a key role in the
pathogenesis of hypertension and pathogenesis of hypertension and atherosclerosis. On atherosclerosis. On the other side the other side
protein or fat ingestion have no significant protein or fat ingestion have no significant sympathoexcitatory sympathoexcitatory effect. effect.


(Koop (Koop W. The W. The atherogenic atherogenic potential of dietary carbohydrate. Preventive Medicine 42 potential of dietary carbohydrate. Preventive Medicine 42
(2006): (2006): 336 336--342; Koop 342; Koop W. Chronically increased activity of the sympathetic nervous W. Chronically increased activity of the sympathetic nervous
system: our diet system: our diet--related evolutionary inheritance. The Journal of Nutrition, Health & related evolutionary inheritance. The Journal of Nutrition, Health &
Aging Volume 13, Number 1, Aging Volume 13, Number 1, 2009; 2009; Welle Welle SS, et al , et al Thermic effect of feeding in men: Thermic effect of feeding in men:
Increased plasma norepinephrine levels following glucose but not protein or fat Increased plasma norepinephrine levels following glucose but not protein or fat
consumption. Metabolism 1981; 30: consumption. Metabolism 1981; 30: 953 953--958; 958; Tentolouris Tentolouris et al. Differential effect of et al. Differential effect of
high high--fat and high carbohydrate fat and high carbohydrate isoenergetic isoenergetic meals on cardiac autonomic nervous meals on cardiac autonomic nervous
system activity system activity in lean in lean and obese women. Metabolism 2003; 52: and obese women. Metabolism 2003; 52: 1426 1426--32) 32)


The The prevalence of coronary artery prevalence of coronary artery disease disease is 3 to 5 times higher in patients is 3 to 5 times higher in patients
with with obstructive seep apnea (OSA) obstructive seep apnea (OSA) compared with control compared with control populations. populations.
Increased carotid intima Increased carotid intima--media media thickness thickness and plaque occurrence was and plaque occurrence was
reported in OSA patients without any other significant co reported in OSA patients without any other significant co--morbidity morbidity
compared to matched compared to matched controls. controls. OSA patients experience intermittent OSA patients experience intermittent
hypoxaemia hypoxaemia and CO2 retention that modify the autonomic and and CO2 retention that modify the autonomic and
haemodynamic haemodynamic responses to responses to sleep. sleep. Chronic intermittent hypoxia may Chronic intermittent hypoxia may
lead to sympathetic lead to sympathetic overactivity overactivity..

(Marin (Marin JM, JM, Carrizo Carrizo SJ, Vicente E, SJ, Vicente E, Agusti Agusti AG. AG. Long Long--term term cardiovascular cardiovascular outcomes outcomes
in in men men with with obstructive obstructive sleep sleep apnoea apnoeahypopnoea hypopnoea with with or or without without treatment treatment with with
continuous continuous positive positive airway airway pressure pressure: : an an observational observational study study. Lancet 2005; 365: . Lancet 2005; 365:
1046 10461053; 1053; Somers Somers VK, VK, Dyken Dyken ME, Mark AL, ME, Mark AL, Abboud Abboud FM. FM. Sympathetic Sympathetic nerve nerve
activity activity during during sleep sleep in normal in normal subjects subjects. N . N Engl Engl J J Med Med 1993; 328 : 1993; 328 : 303 303--7; 7; Johnson, T. Johnson, T.
SS. . and and all all. . Greenberg HE, Greenberg HE, and and all all. . Chronic Chronic intermittent intermittent hypoxia hypoxia increases increases
sympathetic sympathetic responsiveness responsiveness to to hypoxia hypoxia and and hypercapnia hypercapnia. J . J Appl Appl Physiol Physiol 1999; 86: 1999; 86:
298 298305) 305)

Some Some recent studies have demonstrated that coronary atherosclerosis is recent studies have demonstrated that coronary atherosclerosis is
more severe in patients with vascular more severe in patients with vascular erectile dysfunction (ED), erectile dysfunction (ED), with with
indications indications that ED may be an additional, early warning sign of coronary that ED may be an additional, early warning sign of coronary
atherosclerosis. One of these atherosclerosis. One of these has shown that men with idiopathic ED have has shown that men with idiopathic ED have
evidence of endothelial dysfunction in forearm resistance vessels, evidence of endothelial dysfunction in forearm resistance vessels,
increased pulse pressure and impaired heart rate variability. T increased pulse pressure and impaired heart rate variability. The he authors authors
say this say this support the concept that erectile dysfunction is a predictor of support the concept that erectile dysfunction is a predictor of
cardiovascular dysfunction and a precursor of clinical cardiovascular cardiovascular dysfunction and a precursor of clinical cardiovascular
disease. disease. A very recent study has demonstrated that patients with ED A very recent study has demonstrated that patients with ED
exhibited different heart rate variability compared with normal controls, exhibited different heart rate variability compared with normal controls,
confirming the results of other studies showing that patients with ED confirming the results of other studies showing that patients with ED
may have excessive sympathetic may have excessive sympathetic activity. activity.

((Chiurlia Chiurlia E et al. Subclinical coronary artery atherosclerosis in patients with erectile E et al. Subclinical coronary artery atherosclerosis in patients with erectile
dysfunction. J Am dysfunction. J Am Coll Coll Cardiol Cardiol, 2005; , 2005; 46:1503 46:1503--63; Stuckey 63; Stuckey BG, Walsh JP BG, Walsh JP et al. et al.
Erectile dysfunction predicts Erectile dysfunction predicts generalised generalised cardiovascular disease. Evidence from a cardiovascular disease. Evidence from a
case control study. Atherosclerosis 2007, 194(2): case control study. Atherosclerosis 2007, 194(2):458 458--64; Lee 64; Lee JY JY et et al. Heart rate al. Heart rate
variability in men with erectile dysfunction. variability in men with erectile dysfunction. Int Int Neurourol Neurourol J J 2011;15:87 2011;15:87--91) 91)

The The metabolic syndrome is associated with increased risk for metabolic syndrome is associated with increased risk for
development of both cardiovascular disease and type development of both cardiovascular disease and type--2 diabetes in 2 diabetes in
humans. Central obesity and insulin resistance are thought to represent humans. Central obesity and insulin resistance are thought to represent
common underlying factors of the syndrome, which features a chronic common underlying factors of the syndrome, which features a chronic
low low--grade inflammatory state grade inflammatory state . . Several markers of adrenergic drive, such Several markers of adrenergic drive, such
as plasma norepinephrine, norepinephrine spillover from adrenergic as plasma norepinephrine, norepinephrine spillover from adrenergic
nerve terminals, heart rate and others, with sympathetic activation, have nerve terminals, heart rate and others, with sympathetic activation, have
all shown an increase in the different conditions clustering in metabolic all shown an increase in the different conditions clustering in metabolic
syndrome like obesity, hypertension and insulin resistance syndrome like obesity, hypertension and insulin resistance state. state.



((Paoletti Paoletti R, R, Bolego Bolego C, Poli A, C, Poli A, and and Cignarella Cignarella A. A. Metabolic Metabolic Syndrome Syndrome, , Inflammation Inflammation
and and Atherosclerosis Atherosclerosis. . Vasc Vasc Health Health Risk Risk Manag Manag. 2006 . 2006 June June; 2(2): ; 2(2): 145 145152; 152; Mancia Mancia G, G,
Bousquet Bousquet P et al. The P et al. The sympathetic sympathetic nervous nervous system system and and the the metabolic metabolic syndrome syndrome. .
Journal Journal of of Hypertension Hypertension 2007, 25 (5): 2007, 25 (5):909 909--920; Grassi 920; Grassi G, G, Quarti Quarti--Trevano Trevano F et al. F et al.
Cardiovascular Cardiovascular risk risk and and adrenergic adrenergic overdrive overdrive in in metabolic metabolic syndrome syndrome. . Nutr Nutr Metab Metab
Cardiovasc Cardiovasc Dis Dis 2007, 17(6): 2007, 17(6): 473 473--81) 81)



Periodontal Periodontal disease, one the most common chronic bacterial infection, disease, one the most common chronic bacterial infection,
may represent a favorable scenario to verify the connection of infection may represent a favorable scenario to verify the connection of infection
and atherosclerosis/cardiovascular and atherosclerosis/cardiovascular disease. Several disease. Several studies are studies are
suggesting an oral source for atherosclerotic plaque suggesting an oral source for atherosclerotic plaque -- associated bacteria associated bacteria
with demonstration about the presence of viable periodontal pathogens with demonstration about the presence of viable periodontal pathogens
in atherosclerotic in atherosclerotic plaques. plaques. In this regard an interesting hypothesis was In this regard an interesting hypothesis was
proposed in 2004 that periodontal infection may lead to brief episodes of proposed in 2004 that periodontal infection may lead to brief episodes of
bacteremia with inoculation of atherosclerotic plaque by periodontal bacteremia with inoculation of atherosclerotic plaque by periodontal
pathogens pathogens. However, important information is left aside by most . However, important information is left aside by most
investigators studying the connection between oral infection and investigators studying the connection between oral infection and
atherosclerosis/coronary myocardial atherosclerosis/coronary myocardial disease. These investigators dont disease. These investigators dont
take in consideration that the sympathetic nervous system is intensely take in consideration that the sympathetic nervous system is intensely
activated during bacteremia. activated during bacteremia.



((Gaetti Gaetti--Jardim E et al. Jardim E et al. Quantitative Quantitative detection detection of of periodontopathic periodontopathic bacteria bacteria in in
atherosclerotic atherosclerotic plaques plaques from from coronary coronary arteries arteries. J . J Med Med Microbiol Microbiol 58:1568 58:15681575, 2009 1575, 2009; ;
Leinhardt Leinhardt DJ et al. DJ et al. Plasma NE Plasma NE concentrations concentrations do do not not accurately accurately reflect reflect sympathetic sympathetic
nervous nervous system system activity activity in in human human sepsis sepsis. . Am Am J J Physiol Physiol 1993; 1993; 265:E2848; 265:E2848; Straub Straub RH et al. RH et al.
Ablation Ablation of of the the sympathetic sympathetic nervous nervous system system decreases decreases gram gram--negative negative and and increases increases
gram gram--positive positive bacterial bacterial dissemination dissemination: : key key roles for tumor roles for tumor necrosis necrosis factor factor//phagocytes phagocytes
and and interleukin interleukin--4/ 4/lymphocytes lymphocytes. . Infect Infect Dis Dis. 2005 . 2005 Aug Aug 15;192(4): 15;192(4):560 560--72) 72)

There There is is an an intense intense discussion discussion on on the the benefits benefits and and potential potential harm harm of of
reducing reducing salt salt intake intake in in the the general general population population. In . In our our view view, , both both
restriction restriction and and high high salt salt intake intake may may result result in in coronary coronary artery artery disease disease*. The *. The
reason reason is is that that in in both both cases cases exists exists an an increased increased sympathetic sympathetic nerve nerve activity activity. .


(*Book Acidity theory of atherosclerosis (*Book Acidity theory of atherosclerosis New Evidences, by Carlos New Evidences, by Carlos Monteiro Monteiro. .
Chapter: Both Chapter: Both restriction and high salt intake may result in cardiovascular restriction and high salt intake may result in cardiovascular
disease, 2012, Amazon.com; disease, 2012, Amazon.com; Stolarz Stolarz--Skrypek Skrypek K, et al. Fatal and nonfatal outcomes, K, et al. Fatal and nonfatal outcomes,
incidence of incidence of hypertension hypertension, and blood pressure changes in relation to urinary , and blood pressure changes in relation to urinary
sodium excretion. JAMA 2011; sodium excretion. JAMA 2011; 305:1777 305:1777--1785; Guido 1785; Guido Grassi Grassi, et al. Short , et al. Short-- and Long and Long--
Term Term Neuroadrenergic Neuroadrenergic Effects of Moderate Dietary Sodium restriction in Essential Effects of Moderate Dietary Sodium restriction in Essential
Hypertension. Circulation. 2002;106: 1957 Hypertension. Circulation. 2002;106: 1957--1961; 1961; 'Volume 'Volume--expanded expanded' hypertension: ' hypertension:
the effect of fluid overload and the role of the sympathetic nervous system in salt the effect of fluid overload and the role of the sympathetic nervous system in salt--
dependent hypertension, Journal of Hypertension, V30; N1: January dependent hypertension, Journal of Hypertension, V30; N1: January 2012) 2012)


Insomnia is characterized by a constant sympathetic hyper Insomnia is characterized by a constant sympathetic hyper--activation. activation.
In 1999 was hypothesized that insomnia may be related to continual In 1999 was hypothesized that insomnia may be related to continual
stressors, reduced slow stressors, reduced slow--wave sleep, and autonomic dysfunction, which wave sleep, and autonomic dysfunction, which
increase the risk of heart problems. increase the risk of heart problems.


(de (de Zambotti Zambotti M, M, Covassin Covassin N, N, Sarlo Sarlo M, De M, De Min Min Tona G, Tona G, Trinder Trinder J, J, Stegagno Stegagno L. L.
Nighttime cardiac sympathetic hyper Nighttime cardiac sympathetic hyper--activation in young primary insomniacs. activation in young primary insomniacs.
Clin Clin Auton Auton Res Res.. 2013 Feb;23(1):49 2013 Feb;23(1):49--56; Schwartz S, McDowell Anderson W, Cole 56; Schwartz S, McDowell Anderson W, Cole
SR, SR, Cornoni Cornoni--Huntley J, Hays JC, Blazer D. Insomnia and heart disease: a review of Huntley J, Hays JC, Blazer D. Insomnia and heart disease: a review of
epidemiologic studies. J epidemiologic studies. J Psychosom Psychosom Res. 1999 Oct;47(4):313 Res. 1999 Oct;47(4):313--33;) 33;)

Studies have shown that long Studies have shown that long--term marathon runners may have term marathon runners may have
increased coronary calcium and calcified plaque volume. Other studies increased coronary calcium and calcified plaque volume. Other studies
support an increased awareness of atherosclerosis prevalence and support an increased awareness of atherosclerosis prevalence and
cardiovascular risk factors in marathon runners. cardiovascular risk factors in marathon runners.
In our view the sympathetic activation and the resulted increase in blood In our view the sympathetic activation and the resulted increase in blood
lactate levels may represent the biological mechanism leading to lactate levels may represent the biological mechanism leading to
atherosclerosis in marathon runners atherosclerosis in marathon runners.

(Schwartz JG, Merkel (Schwartz JG, Merkel--Kraus S, Duval S, et al. Does elite athleticism enhance or Kraus S, Duval S, et al. Does elite athleticism enhance or
inhibit coronary artery plaque formation. inhibit coronary artery plaque formation. American American College College of of Cardiology Cardiology 2010 2010
Scientific Scientific Sessions Sessions; ; March March 16, 2010; Atlanta, GA; 16, 2010; Atlanta, GA; Kroger K et al. Carotid and Kroger K et al. Carotid and
peripheral atherosclerosis in male marathon runners. Med peripheral atherosclerosis in male marathon runners. Med Sci Sci Sports Sports Exerc Exerc.. 2011 2011
Jul;43(7):1142 Jul;43(7):1142--7; 7; Beth A Taylor Beth A Taylor et et al. al. Influence of chronic exercise on carotid Influence of chronic exercise on carotid
atherosclerosis in marathon runners, atherosclerosis in marathon runners, BMJ Open 2014;4:e004498) BMJ Open 2014;4:e004498)


A A history history of of preeclampsia preeclampsia have have a a higher higher risk risk of of cardiovascular cardiovascular disease disease and and
mortality mortality in in later later life life. . Studies Studies have have shown shown that that women women with with preeclampsia preeclampsia had had
significantly significantly more more atherosclerostic atherosclerostic plaques plaques than than parous parous controls controls. . The The carotid carotid
intima intima--media media thickness thickness in in these these women women with with pre pre--eclampsia eclampsia also also tended tended to to be be
higher higher than than in in other other groups groups..
The The autonomic autonomic nervous nervous system system appears appears to play to play an an important important role in role in the the etiology etiology of of
preeclampsia preeclampsia where where there there is is increased sympathetic and decreased increased sympathetic and decreased
parasympathetic control of heart rate parasympathetic control of heart rate. . The The lactate lactate dehydrogenase dehydrogenase levels levels are are also also
significantly significantly elevated elevated in in women women with with preeclampsia preeclampsia..

((Haukkamaa Haukkamaa L, L, Moilanen Moilanen L, L, Kattainen Kattainen A, A, Luoto Luoto R et al. 2009. Pre R et al. 2009. Pre--eclampsia eclampsia is a risk factor of is a risk factor of
carotid artery atherosclerosis. carotid artery atherosclerosis. Cerebrovasc Cerebrovasc Dis Dis 27(6): 599 27(6): 599--607; 607; Blaauw Blaauw J, van J, van Pampus Pampus MG, MG,
Doormal Doormal JV, et al. 2006. Increased JV, et al. 2006. Increased intima intima--media media--thickness after early onset of preeclampsia. thickness after early onset of preeclampsia.
Obstet Obstet Gynecol Gynecol 107(6): 1345 107(6): 1345--51. N. 51. N. Sharashkina Sharashkina et et al. al. Preeclampsia and pregnancy induced Preeclampsia and pregnancy induced
hypertension and carotid artery atherosclerosis. Pregnancy Hypertension 2012,V2; I3: 294 hypertension and carotid artery atherosclerosis. Pregnancy Hypertension 2012,V2; I3: 294--295; 295;
Yang, Cheryl C. H., Te Yang, Cheryl C. H., Te--Chang Chao et al. Chang Chao et al. Preeclamptic Preeclamptic pregnancy is associated with pregnancy is associated with
increased sympathetic and decreased parasympathetic control of HR. Am J increased sympathetic and decreased parasympathetic control of HR. Am J Physiol Physiol Heart Circ Heart Circ
Physiol Physiol 2000, 2000, 278: 1269 278: 12691273; 1273; He S, He S, Bremme Bremme K, K, Kallner Kallner A, et al. Increased concentrations of A, et al. Increased concentrations of
lactate lactate dehydrogenase dehydrogenase in pregnancy with preeclampsia; a predictor for birth of small for in pregnancy with preeclampsia; a predictor for birth of small for
gestational age infants. gestational age infants. Gynecol Gynecol Obstet Obstet Invest. 1995;39:234 Invest. 1995;39:2348; 8; Catanzerite VA, Steinberg SM, Catanzerite VA, Steinberg SM,
Mosley CA, et al. Severe Mosley CA, et al. Severe preeclampsia with preeclampsia with fulminant fulminant and extreme elevation of and extreme elevation of aspartate aspartate
aminotransferase aminotransferase and and lactate lactate dehydrogenase dehydrogenase levels levels. . Am Am J J Perinatol Perinatol. 1995;12:310 . 1995;12:3103) 3)



Hyperhomocysteinemia Hyperhomocysteinemia has been reported to be associated with both has been reported to be associated with both
vascular structure alteration and increased cardiovascular risk. vascular structure alteration and increased cardiovascular risk.
Some studies have shown a relationship Some studies have shown a relationship between between homocysteine homocysteine and and
psychological risk factors for cardiovascular diseases, like hostility and psychological risk factors for cardiovascular diseases, like hostility and
anger. However, a subsequent study revealed that there anger. However, a subsequent study revealed that there is no evidence is no evidence
for an association between for an association between homocysteine homocysteine levels and cardiovascular levels and cardiovascular
autonomic function in either diabetic or autonomic function in either diabetic or nondiabetic nondiabetic subjects. subjects. So, So,
according this later study the cardiovascular according this later study the cardiovascular autonomic dysfunction does autonomic dysfunction does
not help not help to explain to explain why why hyperhomocysteinaemia hyperhomocysteinaemia is related to is related to
cardiovascular mortality cardiovascular mortality..
My take on the biological mechanism is that My take on the biological mechanism is that homocysteine homocysteine and its acidic and its acidic
derivatives might contribute to the acidic coronary blood flow that lead derivatives might contribute to the acidic coronary blood flow that lead to to
increased increased perfusion pressure perfusion pressure and and effects on contractility of coronary effects on contractility of coronary
arteries, arteries, resulting in resulting in changes in hemodynamic shear stress changes in hemodynamic shear stress that ends in that ends in
atherosclerosis/coronary myocardial disease. atherosclerosis/coronary myocardial disease.


((Stoney Stoney CM, CM, Engebretson Engebretson TO. TO. Plasma Plasma homocysteine homocysteine concentrations are positively concentrations are positively
associated with hostility and anger. Life Sci. 2000;66(23): associated with hostility and anger. Life Sci. 2000;66(23):2267 2267--75 75; ; Spoelstra Spoelstra--De Man De Man
AM, AM, Smulders Smulders YM et al. YM et al. Homocysteine Homocysteine levels are not associated with levels are not associated with
cardiovascular autonomic function in elderly Caucasian subjects without or with cardiovascular autonomic function in elderly Caucasian subjects without or with
type 2 diabetes mellitus: the Hoorn Study type 2 diabetes mellitus: the Hoorn Study.. J Intern Med. 2005 Dec;258(6):536 J Intern Med. 2005 Dec;258(6):536--43 43.) .)

The The studies studies associating associating cardiovascular cardiovascular disease disease with with the the exposition exposition to to
certain certain chemicals chemicals like like perfluorooctanoic perfluorooctanoic acid acid , , arsenic arsenic, lead , lead and and cadmium cadmium
besides some persistent organic pollutants, besides some persistent organic pollutants, reminds reminds me me the the experiments experiments
from from the the beginning beginning of of the the last last century century showing showing that that acid acid--fed fed rabbits rabbits and and
dogs dogs develop develop atherosclerotic atherosclerotic lesions lesions. In . In our our opinion opinion the the effects effects generating generating
atherosclerotic atherosclerotic lesions lesions in in these these experiments experiments were were caused caused not not only only by by
chronic chronic hyperacidity hyperacidity in in rabbits rabbits and and dogs dogs but but also also related related to to an an intense intense
activation activation of of the the sympathetic sympathetic system system provoked provoked by by acid acid ingestion ingestion..

((Shankar Shankar A, A, Xiao Xiao J, J, Ducatman Ducatman A. A. Perfluorooctanoic Perfluorooctanoic Acid Acid and and Cardiovascular Cardiovascular Disease Disease in in
US US Adults Adults. . Archives Archives of of Internal Internal Medicine, 2012; Medicine, 2012; Hsieh Hsieh YC, YC, Lien Lien LM et al. LM et al. Significantly Significantly
increased increased risk risk of of carotid carotid atherosclerosis atherosclerosis with with arsenic arsenic exposure exposure and and polymorphisms polymorphisms in in
arsenic arsenic metabolism metabolism genes. genes. Environ Environ Res. 2011 Aug;111(6): Res. 2011 Aug;111(6):804 804--10; 10; Revis Revis NW, NW, Zinsmeister Zinsmeister
AR, Bull R. Atherosclerosis and hypertension induction by lead and cadmium ions: an AR, Bull R. Atherosclerosis and hypertension induction by lead and cadmium ions: an
effect prevented by calcium ion. Proc effect prevented by calcium ion. Proc Natl Natl Acad Acad Sci Sci USA 1981; 78 : 6494 USA 1981; 78 : 6494--8; 8; Messner Messner B, B,
Knoflach Knoflach M, M, Seubert Seubert A, A, Ritsch Ritsch A, A, Pfaller Pfaller K, Henderson B, et al. Cadmium is a novel and K, Henderson B, et al. Cadmium is a novel and
independent risk factor for early atherosclerosis mechanisms and in vivo relevance. independent risk factor for early atherosclerosis mechanisms and in vivo relevance.
Arterioscler Arterioscler Thromb Thromb Vasc Vasc Biol Biol 2009; 2009; 29: 29: 1392 1392 1398; P. Monica Lind, Bert van 1398; P. Monica Lind, Bert van Bavel Bavel, ,
Samira Samira Salihovic Salihovic and Lars Lind. Circulating Levels of Persistent Organic Pollutants and Lars Lind. Circulating Levels of Persistent Organic Pollutants
(POPs) and Carotid Atherosclerosis in the Elderly. Environ Health (POPs) and Carotid Atherosclerosis in the Elderly. Environ Health Perspect Perspect 120:38 120:3843 43
(2012); (2012); Loeb Loeb, O., , O., Ueber Ueber experimentelle experimentelle Arterienveraender Arterienveraender ungen ungen mit mit besonderer besonderer
Beruecksichtigung Beruecksichtigung der der Wirkung Wirkung der der Milchsaeure Milchsaeure auf auf Grund Grund eigener eigener Versuche Versuche, , Deutsch Deutsch. .
med. med. Wchnschr Wchnschr., I913, ., I913, xxxix xxxix, I819; I. Adler, , I819; I. Adler, Studies Studies in Experimental in Experimental atherosclerosis atherosclerosis -- A A
preliminary preliminary report report, The , The Journal Journal of of Experimental Medicine, Experimental Medicine, 1913) 1913)



Studies Studies also also suggest suggest that that chemotherapy chemotherapy may may be be a a risk risk factor factor for for the the
development development of of atherosclerosis atherosclerosis. .

((Sajima Sajima T, T, Tanabe Tanabe A A et et al. al. Impact Impact of of platinum platinum--based based chemotherapy chemotherapy on on the the
progression progression of of atherosclerosis atherosclerosis. . Climateric Climateric 2011 2011 Feb Feb;14 (1): 31 ;14 (1): 31--40; 40; Kalabova Kalabova H, H,
Melichar Melichar B B et et al. Intima al. Intima--media media thickness thickness, , myocardial myocardial perfusion perfusion and and laboratory laboratory risk risk
factors factors of of atherosclerosis atherosclerosis in in patients patients with with breast breast cancer cancer treated treated with with anthracycline anthracycline--
based based chemotherapy chemotherapy. . Med Med Oncol Oncol 2011 2011 Dec Dec; 28 (4): 1281 ; 28 (4): 1281--7) 7)


Radiation Radiation may may also also induce induce atherosclerosis atherosclerosis. . Recent Recent epidemiological epidemiological
studies studies provided provided evidence evidence that that an an excess excess risk risk of of cardiovascular cardiovascular disease disease
can can be be associated associated with with moderate moderate and and low low dose dose radiation radiation..

It is It is reconized reconized for more for more than than 50 50 years years the the effects effects of of radiation radiation over over the the
nervous nervous system. In system. In this this relationship relationship W. O W. O Caster Caster from from US US said said in a in a
Symposium Symposium on on the the Effects Effects of of Ionizing Ionizing Radiation Radiation on on the the Nervous Nervous System System
held held by by the the International International Atomic Atomic Energy Energy Agency Agency (IAEA), in 1961: (IAEA), in 1961:

it it may may turn turn out out that that a central a central nervous nervous system system response response is is an an important important
underlying underlying factor factor in in the the causation causation of of many many of of the the common common manifestations manifestations of of
radiation radiation damage damage

(Andrea (Andrea Borghini Borghini et et al. al. Ionizing radiation and atherosclerosis: Current knowledge Ionizing radiation and atherosclerosis: Current knowledge
and future challenges. Atherosclerosis 2013, V 230; I 1: 40 and future challenges. Atherosclerosis 2013, V 230; I 1: 40 47) 47)


Recent studies show that acute myocardial infarction leads to acceleration Recent studies show that acute myocardial infarction leads to acceleration
of atherosclerosis. In our view this happens because the acute of atherosclerosis. In our view this happens because the acute
sympathetic activity in AMI results in lactic acidosis and lactate sympathetic activity in AMI results in lactic acidosis and lactate
accumulation leading to increased perfusion pressure and effects on accumulation leading to increased perfusion pressure and effects on
contractility of coronary arteries ,with changes in hemodynamic shear contractility of coronary arteries ,with changes in hemodynamic shear
stress ending in atherosclerosis as consequence. Mechanism supported by stress ending in atherosclerosis as consequence. Mechanism supported by
the acidity theory of atherosclerosis. the acidity theory of atherosclerosis.

((Dutta Dutta P, P, Courties Courties G, G, Wei Wei Y, Y, Leuschner Leuschner F, F, Gorbatov Gorbatov R, Robbins CS, Iwamoto Y, R, Robbins CS, Iwamoto Y, et et
al. al. Myocardial Myocardial infarction infarction accelerates accelerates atherosclerosis atherosclerosis. . Nature Nature. 2012 Jul . 2012 Jul
19;487(7407):325 19;487(7407):325--9; 9; Hui Hui Wang, Daniel T. Wang, Daniel T. Eitzman Eitzman. Acute myocardial infarction . Acute myocardial infarction
leads to acceleration of atherosclerosis. Atherosclerosis, Volume 229, Issue 1 , Pages leads to acceleration of atherosclerosis. Atherosclerosis, Volume 229, Issue 1 , Pages
18 18--22, July 2013) 22, July 2013)


In In addition of diabetes and hypertension there are various diseases addition of diabetes and hypertension there are various diseases
associated with associated with atherosclerosis/coronary artery disease atherosclerosis/coronary artery disease where the where the
common denominator is the elevation of lactic acid or lactate, for common denominator is the elevation of lactic acid or lactate, for
example: psoriasis, rheumatoid example: psoriasis, rheumatoid arthritis, osteoporosis arthritis, osteoporosis and migraine. and migraine.
Certainly the raise in lactic acid/lactate levels might also Certainly the raise in lactic acid/lactate levels might also be related be related to to an an
altered autonomic nervous system with sympathetic predominance. altered autonomic nervous system with sympathetic predominance.

(Stephen O Crawford et al, Association of blood lactate with type 2 diabetes: the (Stephen O Crawford et al, Association of blood lactate with type 2 diabetes: the
Atherosclerosis Risk in Communities Carotid MRI Study. International Journal of Atherosclerosis Risk in Communities Carotid MRI Study. International Journal of
Epidemiology 2010;1 Epidemiology 2010;19; F. E. 9; F. E. Demartini Demartini, P. J. Cannon, W. B. , P. J. Cannon, W. B. Stason Stason, and J. H. , and J. H. Laragh Laragh. .
Lactic Acid Metabolism in Hypertensive Patients. Science 11 June 1965, Vol. 148. no. Lactic Acid Metabolism in Hypertensive Patients. Science 11 June 1965, Vol. 148. no.
3676; 3676; Gelfand Gelfand JM. Patients with severe psoriasis are at increased risk of cardiovascular JM. Patients with severe psoriasis are at increased risk of cardiovascular
mortality: cohort study using the General Practice mortality: cohort study using the General Practice Research Database Research Database. . Eur Eur Heart J. 2009 Heart J. 2009
Dec 27.; Dec 27.; Malina Malina L, L, Volek Volek V, V, Bielicky Bielicky T. The activity of lactate dehydrogenase in the T. The activity of lactate dehydrogenase in the
erythrocytes in psoriasis. Z Haut erythrocytes in psoriasis. Z Haut Geschlechtskr Geschlechtskr. 1969 Oct 1;44(19):877 . 1969 Oct 1;44(19):877--9; Roman M. J, et 9; Roman M. J, et
al. Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern al. Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern
Med. 2006; 144: 249 Med. 2006; 144: 249--256; 256; Gobelet Gobelet C and C and Gerster Gerster J. C. Synovial fluid lactate levels in septic J. C. Synovial fluid lactate levels in septic
and non and non--septic septic arthritides arthritides. Annals of the Rheumatic diseases, 1984, 43, 742 . Annals of the Rheumatic diseases, 1984, 43, 742--745; 745; Dekkers Dekkers
JC et al. Elevated sympathetic nervous system activity in patients with recently JC et al. Elevated sympathetic nervous system activity in patients with recently
diagnosed rheumatoid arthritis with active disease. diagnosed rheumatoid arthritis with active disease. Clin Clin Exp Exp Rheumatol Rheumatol. 2004 Jan . 2004 Jan--
Feb;22(1):63 Feb;22(1):63--70. 70. Larus Larus S S Gudmundsson Gudmundsson, Ann I , Ann I Scher Scher, Thor , Thor Aspelund Aspelund, et al. Migraine , et al. Migraine
with aura and risk of cardiovascular and all cause mortality in men and women: with aura and risk of cardiovascular and all cause mortality in men and women:
prospective cohort study, BMJ 2010;341:c3966; Okada H, prospective cohort study, BMJ 2010;341:c3966; Okada H, Araga Araga S, S, Takeshima Takeshima T, T,
Nakashima K. Plasma lactic acid and pyruvic acid levels in migraine and tension Nakashima K. Plasma lactic acid and pyruvic acid levels in migraine and tension--type type
headache. Headache. 1998 Jan;38(1):39 headache. Headache. 1998 Jan;38(1):39--42) 42)


Different Different necropsy studies have shown that the occurrence of necropsy studies have shown that the occurrence of
atherosclerosis atherosclerosis is milder or non is milder or non--existent in subjects with Down existent in subjects with Down syndrome. syndrome.
A A reasonable explanation for the reduced incidence of reasonable explanation for the reduced incidence of atherosclerosis atherosclerosis is is
the altered autonomic regulation in individuals with DS, with effects of the altered autonomic regulation in individuals with DS, with effects of
smaller changes in smaller changes in baroreflex baroreflex sensitivity and in sensitivity and in sympatho sympatho--excitation excitation
response. response. The reduced sympathetic response to stress in DS is supported The reduced sympathetic response to stress in DS is supported
by the low circulating by the low circulating catecholamines catecholamines levels in response to incremental levels in response to incremental
cycle cycle ergometer exercise in individuals with ergometer exercise in individuals with DS. DS.

((Yl Yl--Herttuala Herttuala S, S, Luoma Luoma J, J, Nikkari Nikkari T, T, Kivimki Kivimki T. Down's syndrome and T. Down's syndrome and
atherosclerosis. atherosclerosis. Atherosclerosis, Atherosclerosis, 1989 Apr;76(2 1989 Apr;76(2--3): 3):269 269--72; Murdoch 72; Murdoch JC, Rodger JC, JC, Rodger JC,
Rao Rao SS, Fletcher CD, SS, Fletcher CD, Dunnigan Dunnigan MG. Down's syndrome: an atheroma MG. Down's syndrome: an atheroma--free model? free model?
Br Med J. 1977 Jul 23;2(6081): Br Med J. 1977 Jul 23;2(6081):226 226--8; 8; Iellamo Iellamo F, F, Galante Galante A, et al. Altered autonomic A, et al. Altered autonomic
cardiac regulation in cardiac regulation in individuals individuals with Down syndrome. Am J with Down syndrome. Am J Physiol Physiol Heart Heart Circ Circ
Physiol. Physiol. 2005 Dec;289(6 2005 Dec;289(6): ):H2387 H2387--91; Bo 91; Bo Fernhall Fernhall and Mari and Mari Otterstetter Otterstetter. Attenuated . Attenuated
responses to responses to sympatho sympatho--excitation in individuals with Down syndrome. J excitation in individuals with Down syndrome. J Appl Appl
Physiol Physiol 94: 2158 94: 21582165, 2003); 2165, 2003); Eberhard Eberhard Y, Y, Etarradossi Etarradossi J and J and Terminarias Terminarias A. A.
Biochemical changes and catecholamine response in Downs syndrome adolescents Biochemical changes and catecholamine response in Downs syndrome adolescents
in relation to incremental maximal exercise. J in relation to incremental maximal exercise. J Ment Ment Defic Defic Res 35: 140 Res 35: 140--146, 146, 1991) 1991)

Necropsy studies have shown that individuals Necropsy studies have shown that individuals suffering from alcoholism suffering from alcoholism
have a significantly have a significantly lower degree of atherosclerosis in the coronary lower degree of atherosclerosis in the coronary
arteries. arteries.
A paper published in 2002 may have the answer to this question. William A paper published in 2002 may have the answer to this question. William
Lovallo Lovallo, one of the authors of this , one of the authors of this paper, paper, told in interview to told in interview to EurekAlert EurekAlert
that::Before testing alcoholics for their responses to a public that::Before testing alcoholics for their responses to a public--speaking speaking
task, researchers first needed to establish if their sympathetic nervous task, researchers first needed to establish if their sympathetic nervous
system was able to respond at all. "This would tell us if their blunting was system was able to respond at all. "This would tell us if their blunting was
specific to psychological stressors like public speaking," said specific to psychological stressors like public speaking," said Lovallo Lovallo, "or , "or
due to a generalized autonomic deficit." due to a generalized autonomic deficit."
The The patients reacted as if the social challenge of public speaking had no patients reacted as if the social challenge of public speaking had no
special meaning for them. So, the sympathetic nervous system in the special meaning for them. So, the sympathetic nervous system in the
patients looked normal, but their response to a psychological stressor was patients looked normal, but their response to a psychological stressor was
almost absent. When faced with a socially meaningful stressor, neither almost absent. When faced with a socially meaningful stressor, neither
part of their fight part of their fight--flight mechanism was working flight mechanism was working." ."


((Leary Leary T. T. Atherosclerosis Atherosclerosis, , the the important important form form of of arteriosclerosis arteriosclerosis, a , a metabolic metabolic
disease disease. . Vol Vol 104, N7. JAMA, 104, N7. JAMA, 1935; 1935; Thomsen Thomsen JL. JL. Atherosclerosis Atherosclerosis in in alcoholics alcoholics. .
Forensic Forensic Sci Sci Int. 1995 Int. 1995 Oct Oct 30;75(2 30;75(2--3):121 3):121--31 31 and and in in Ugeskr Ugeskr Laeger Laeger. 1997 . 1997 Feb Feb
3;159(6):757 3;159(6):757--60; 60; Tera Tera L. L. Panknin Panknin, Stacey L. , Stacey L. Dickensheets Dickensheets, Sara J. Nixon, William R. , Sara J. Nixon, William R.
Lovallo Lovallo. . Attenuated Attenuated Heart Rate Responses Heart Rate Responses to to Public Public Speaking Speaking in in Individuals Individuals With With
Alcohol Alcohol Dependence Dependence. . Alcohol Alcohol Clin Clin. Exp. Res. 2002 . Exp. Res. 2002 Jun Jun; 26 (6): 841 ; 26 (6): 841

Studies Studies have shown that rhesus monkeys submitted to sympatholytic agents have shown that rhesus monkeys submitted to sympatholytic agents
like like betablockers betablockers or bilateral surgical thoracic or bilateral surgical thoracic sympathectomy sympathectomy have had a have had a
marked reduction in the progression of marked reduction in the progression of atherosclerosis. The atherosclerosis. The first randomized first randomized
trial showing that trial showing that betablockers betablockers can reduce the rate of progression of carotid can reduce the rate of progression of carotid
IMT in clinically healthy symptom IMT in clinically healthy symptom--free subjects with carotid plaque was free subjects with carotid plaque was
published in published in 2001. A 2001. A recent pooled analysis data from 4 intravascular recent pooled analysis data from 4 intravascular
ultrasonography trials involving 1,515 patients has confirmed that ultrasonography trials involving 1,515 patients has confirmed that betablocker betablocker
therapy is associated with reduced atheroma therapy is associated with reduced atheroma progression. A progression. A study by Strawn study by Strawn
and colleagues in 1991 have indicated that social disruption is associated with and colleagues in 1991 have indicated that social disruption is associated with
both sympathetic nervous system arousal and indexes of endothelial both sympathetic nervous system arousal and indexes of endothelial
dysfunction, effects that may be prevented by dysfunction, effects that may be prevented by treatment treatment with B with B--adrenergic adrenergic
blocking agent. blocking agent. Also interesting is the study showing a decrease in Also interesting is the study showing a decrease in
glycogenolytic glycogenolytic rate, blood lactate concentration and lactate clearance after B rate, blood lactate concentration and lactate clearance after B--
Adrenergic blockade with Adrenergic blockade with propranolol propranolol, probable a indirect effect of its , probable a indirect effect of its
sympatholytic sympatholytic properties. properties.

((Lichtor Lichtor T et al. 1987.The T et al. 1987.The sympathetic sympathetic nervous nervous system system and and atherosclerosis atherosclerosis. J . J Neurosurg Neurosurg Dec;67(6): Dec;67(6):906 906--
14; 14; Hedblad Hedblad B et al. B et al. Low Low--dose dose metoprolol metoprolol CR/XL CR/XL and and fluvastatin fluvastatin slow slow progression progression of of carotid carotid intima intima--
media media thickness thickness: : Main Main results results from from the the Beta Beta--Blocker Blocker Cholesterol Cholesterol--Lowering Lowering Asymptomatic Asymptomatic Plaque Plaque
Study Study (BCAPS). (BCAPS). Circulation Circulation. 2001 . 2001 Apr Apr 3;103(13): 3;103(13):1721 1721--6.; 6.; Sipahi Sipahi I et al. 2007. I et al. 2007. BB--Blockers Blockers and and
progression progression of of coronary coronary atherosclerosis atherosclerosis; ; Pooled Pooled analysis analysis of of 4 intravascular 4 intravascular trials trials. . Annals Annals of of Internal Internal
Medicine, 3 July, V147; Medicine, 3 July, V147; Issue Issue 1: 1: 10 10--18; 18; Strawn Strawn WB WB and and all all. . Endothelial Endothelial dysfunction dysfunction in response in response to to
psychosocial psychosocial stress in stress in monkeys monkeys. . Circulation Circulation Research 1991; 68:1270 Research 1991; 68:1270--1279; 1279; Issekutz Issekutz B Jr. Effect of beta B Jr. Effect of beta
adrenergic blockade on lactate turnover in exercising dogs. J adrenergic blockade on lactate turnover in exercising dogs. J Appl Appl Physiol Physiol 1984; 57: 1754 1984; 57: 175459) 59).


To our knowledge only one angiographic study assessed data on regression To our knowledge only one angiographic study assessed data on regression
(15%), inalterability (62%) or progression (23%) of atherosclerosis in patients (15%), inalterability (62%) or progression (23%) of atherosclerosis in patients
treated with cardiac glycosides. Indeed, cardiac glycosides at low treated with cardiac glycosides. Indeed, cardiac glycosides at low
concentration may lead to stress reduction by the improvement of concentration may lead to stress reduction by the improvement of
baroreceptor baroreceptor function, function, sympathoinhibitory sympathoinhibitory effects, effects, vagomimetic vagomimetic effects and effects and
decrease in heightened secretion of decrease in heightened secretion of catecholamines catecholamines..
There are studies showing the existence of potential positive effects of cardiac There are studies showing the existence of potential positive effects of cardiac
glycosides ( glycosides (digoxin digoxin, , digitoxin digitoxin, etc) for the treatment of atherosclerosis. , etc) for the treatment of atherosclerosis.

(Mesquita (Mesquita QHde QHde, , et et al. Preservao funcional do miocrdio isqumico pelo al. Preservao funcional do miocrdio isqumico pelo cardiotonico cardiotonico
a longo prazo: a longo prazo: recateterizao recateterizao de 29 casos. Medicina de Hoje, maro 1978). de 29 casos. Medicina de Hoje, maro 1978). Gheorghiade Gheorghiade
M, Adams KF, M, Adams KF, Colucci Colucci WS. WS. Digoxin Digoxin in the Management of Cardiovascular Disorders in the Management of Cardiovascular Disorders
2004 2004; ; 109 109: : 2959 2959--2964; 2964; Jagielska Jagielska J. et al. J. et al. Digitoxin Digitoxin elicits anti elicits anti--inflammatory and inflammatory and
vasoprotective vasoprotective properties in endothelial cells: Therapeutic implications for the treatment properties in endothelial cells: Therapeutic implications for the treatment
of atherosclerosis?, Atherosclerosis 2009 Oct;206(2):390 of atherosclerosis?, Atherosclerosis 2009 Oct;206(2):390--6; 6; Kolkhof Kolkhof P et al. Cardiac P et al. Cardiac
glycosides potently inhibit C glycosides potently inhibit C--reactive protein synthesis in human reactive protein synthesis in human hepatocytes hepatocytes. . Biochem Biochem
Biophys Biophys Res Res Commun Commun. 2010 Mar 26;394(1): 233 . 2010 Mar 26;394(1): 233--9) 9)

RRegression of egression of coronary coronary atherosclerosis atherosclerosis in women who were free of in women who were free of stress stress
showed through the use of serial quantitative angiography; showed through the use of serial quantitative angiography;
DDecrease of ecrease of carotid carotid intima media thickness intima media thickness in African Americans with in African Americans with
hypertension submitted to stress reduction through Transcendental hypertension submitted to stress reduction through Transcendental
Meditation Meditation ; ;
Decrease Decrease in carotid in carotid intima media thickness in intima media thickness in older persons with multiple older persons with multiple
factors for coronary heart disease submitted to the Maharishi factors for coronary heart disease submitted to the Maharishi Vedic Vedic
Medicine Medicine treatment treatment -- -- which also includes stress reduction through which also includes stress reduction through
Transcendental Meditation Transcendental Meditation program; program;
Yoga Yoga intervention retards progression and increases regression of intervention retards progression and increases regression of
coronary atherosclerosis in patients with severe coronary artery disease coronary atherosclerosis in patients with severe coronary artery disease ..
Slow breathing increases Slow breathing increases baroreflex baroreflex sensitivity and reduce sympathetic sensitivity and reduce sympathetic
nervous system with beneficial effects to coronary myocardial disease. nervous system with beneficial effects to coronary myocardial disease.



*Carlos *Carlos ETB ETB Monteiro Monteiro, Acidic environment evoked , Acidic environment evoked by chronic by chronic stress: A novel stress: A novel
mechanism to explain mechanism to explain atherogenesis atherogenesis. Available . Available from Infarct from Infarct Combat Project, Combat Project,
January 28, 2008 January 28, 2008 at http at http:// ://www.infarctcombat.org/AcidityTheory.pdf; Book www.infarctcombat.org/AcidityTheory.pdf; Book
Acidity Theory of Atherosclerosis: New Evidences, 2012 Acidity Theory of Atherosclerosis: New Evidences, 2012

It It is interesting to notice is interesting to notice about the about the impairment or decrease of impairment or decrease of baroreflex baroreflex
sensitivity sensitivity in front of some key factors for atherosclerosis, in front of some key factors for atherosclerosis, coronary coronary
myocardial disease myocardial disease and stroke, like in ageing, ingestion of sugars, and stroke, like in ageing, ingestion of sugars, in in
special special high high--fructose diets, and smoking. fructose diets, and smoking. Indeed there Indeed there are some studies are some studies
showing that in bilateral carotid atherosclerosis and in greater intima showing that in bilateral carotid atherosclerosis and in greater intima--
media thickness the media thickness the baroreflex baroreflex sensitivity is reduced or impaired sensitivity is reduced or impaired..
On the other hand the result of the baroreceptor improvement On the other hand the result of the baroreceptor improvement is the is the
inhibition of the sympathetic nervous system and activation inhibition of the sympathetic nervous system and activation of the of the
parasympathetic nervous parasympathetic nervous system. system. Drugs Drugs like like Betablockers Betablockers and Digitalis and Digitalis
glycosides may glycosides may enhance enhance baroreflex baroreflex sensitivity sensitivity with with possible positive possible positive
effects on effects on atherosclerosis. atherosclerosis.

(Nasr (Nasr N et al. N et al. Baroreflex Baroreflex sensitivity is impaired in bilateral carotid sensitivity is impaired in bilateral carotid atherosclerosis. atherosclerosis.
Stroke;36:1891 Stroke;36:1891--1895; 1895; Gianoros Gianoros PJ et al. Greater intima PJ et al. Greater intima--media thickness in the media thickness in the
carotid bulb carotid bulb is associated is associated with reduced with reduced baroreflex baroreflex sensitivity. Am J sensitivity. Am J Hypertens Hypertens. .
2002;15(6 2002;15(6): ): 486 486--491 491; ; Truijen Truijen J et al. J et al. Baroreflex Baroreflex sensitivity is higher during acute sensitivity is higher during acute
psychological stress psychological stress in healthy subjects under B in healthy subjects under B--adrenergic blockade. adrenergic blockade. Clin Clin Sci Sci
((Lond Lond), Feb 2011; 120(4):161 ), Feb 2011; 120(4):161--167; 167; Schobel Schobel HP et al. 1991.Contrasting effects of HP et al. 1991.Contrasting effects of
digitalis and digitalis and dobutamine dobutamine on on baroreflex baroreflex sympathetic control in normal humans, sympathetic control in normal humans,
Circulation Circulation V84,1118 V84,1118--1129 1129..

A recent study confirm that the use of beta blockers do not appear to be of any A recent study confirm that the use of beta blockers do not appear to be of any
benefit in three distinct groups of stable outpatients: those with coronary artery benefit in three distinct groups of stable outpatients: those with coronary artery
disease but no history of MI; those with a remote history of MI (one year or more); disease but no history of MI; those with a remote history of MI (one year or more);
and those with coronary risk factors only. and those with coronary risk factors only.
Also, the effect of Also, the effect of betablockers betablockers as a treatment for primary hypertension has been as a treatment for primary hypertension has been
questioned. In a meta questioned. In a meta--analysis study published at Lancet Journal in 2005 the analysis study published at Lancet Journal in 2005 the
authors say that the effect of authors say that the effect of betablockers betablockers compared to placebo is less than compared to placebo is less than
optimum, with no difference for myocardial infarction but with a raised risk of optimum, with no difference for myocardial infarction but with a raised risk of
stroke. stroke.
Moreover in a randomized trial study published in Lancet Journal in 2008 the Moreover in a randomized trial study published in Lancet Journal in 2008 the
authors say that there were more deaths in the authors say that there were more deaths in the metoprolol metoprolol group than in the group than in the
placebo group in patients undergoing non placebo group in patients undergoing non--cardiac surgery (129 versus 97 patients). cardiac surgery (129 versus 97 patients).

So, while So, while betablockers betablockers seems useful in atherosclerosis its poor results in these seems useful in atherosclerosis its poor results in these
clinical situations might be related to their effects of generalized clinical situations might be related to their effects of generalized hypocontractility hypocontractility, ,
as suggested by Dr. as suggested by Dr. Mesquita Mesquita in 1979. in 1979.

(Bangalore S, (Bangalore S, Steg Steg PHG, PHG, Deedwania Deedwania P, et al. Beta blocker use and clinical outcomes in stable P, et al. Beta blocker use and clinical outcomes in stable
outpatients with and without coronary artery disease. JAMA 2012; 308:1340 outpatients with and without coronary artery disease. JAMA 2012; 308:1340--1349; 1349; Lindholm Lindholm
LH, LH, Carlberg Carlberg B, Samuelsson O. Should B blockers remain first choice in the treatment of B, Samuelsson O. Should B blockers remain first choice in the treatment of
primary hypertension? A meta primary hypertension? A meta--analysis. Lancet 2005;366:1545 analysis. Lancet 2005;366:1545--53; POISE study group. Effects 53; POISE study group. Effects
of extended of extended--release release metoprolol metoprolol succinate succinate in patients undergoing non in patients undergoing non--cardiac surgery (POISE cardiac surgery (POISE
Trial): a randomized controlled trial. Lancet 2008; 371: 1839 Trial): a randomized controlled trial. Lancet 2008; 371: 1839--47; 47; Mesquita Mesquita, QH, Book , QH, Book
Myogenic Myogenic Theory of Myocardial Infarction, 1979) Theory of Myocardial Infarction, 1979)


Baldness Baldness
SSevere evere vertex pattern of vertex pattern of androgenetic androgenetic alopecia is considered to have an alopecia is considered to have an
increased risk of subclinical atherosclerosis increased risk of subclinical atherosclerosis. .
There is a postulation made in 1997 by Marino There is a postulation made in 1997 by Marino Salin Salin, from Italy, telling if , from Italy, telling if
there is excess adrenergic tone in the metabolic system, then there is also there is excess adrenergic tone in the metabolic system, then there is also
vasoconstriction, ischemia and hypoxia and if there is hypoxia, vasoconstriction, ischemia and hypoxia and if there is hypoxia, glycolysis glycolysis
leads to lactic acid that causes caustic damage to the inner sheath and this leads to lactic acid that causes caustic damage to the inner sheath and this
sheath seems to be raised above the hair cuticle. sheath seems to be raised above the hair cuticle.

Earlobe Crease Earlobe Crease
Diagonal earlobe crease is another external marker for coronary artery Diagonal earlobe crease is another external marker for coronary artery
disease. Interesting is that the earlobe is one local to determine blood disease. Interesting is that the earlobe is one local to determine blood
lactate concentration that may be in our opinion the culprit for the earlobe lactate concentration that may be in our opinion the culprit for the earlobe
wrinkle. wrinkle.


(Dogramaci AC et al. Is androgenetic alopecia a risk for atherosclerosis? J Eur Acad
Dermatol Venereol. 2009 Jun;23(6):673-7.; Marino Salin e Andrea Marliani,,
TricoItalia (Firenze) marzo 1997, Bolletino della Societ Italiana di Tricologia, La
Teoria e la Clinica delle Incidenze nelle Alopecie. Cumberland GD et al. Earlobe
creases and coronary atherosclerosis. The view from forensic pathology. Am J
Forensic Med Pathol. 1987 Mar;8(1):9-11)



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explanations explanations of of
atherosclerosis atherosclerosis, , under under the the
acidity acidity theory theory point point of of view view..

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