Acidity Theory of Atherosclerosis

TheThe AcidityAcidity TheoryTheory ofof
AtherosclerosisAtherosclerosis
Fourth International Conference on
Advanced Cardiac Sciences
KingKing ofof OrgansOrgans, 2012, 2012
KingdomKingdom ofof SaudiSaudi ArabiaArabia
Carlos MonteiroCarlos Monteiro
InfarctInfarct CombatCombat ProjectProject
http://infarctcombat.orghttp://infarctcombat.org

 In July 29, 2006, during a discussion in the internal forum at internet ofIn July 29, 2006, during a discussion in the internal forum at internet of
the International Network of Cholesterol Skeptics (THINCS) , about thethe International Network of Cholesterol Skeptics (THINCS) , about the
role of mechanical forces in atherosclerosis, Melchior Meijer, a journalistrole of mechanical forces in atherosclerosis, Melchior Meijer, a journalist
specialized in medical area, noticed about the demonstration by scientistsspecialized in medical area, noticed about the demonstration by scientists
from California that normal stretching/relaxing of an artery does notfrom California that normal stretching/relaxing of an artery does not
produce atherosclerosis, while stretching/relaxing in different directionsproduce atherosclerosis, while stretching/relaxing in different directions
simultaneously on every heart beat does.simultaneously on every heart beat does.
 Dr. PaulDr. Paul RoschRosch, 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 friendthat in relation of the contribution of psychological stress his friend
MeyerMeyer TexonTexon, the, the developer of the hemodynamic theory ofdeveloper of the hemodynamic theory of
atherosclerosis,atherosclerosis, concededconceded to him into him in aa conversation that stress mightconversation that stress might
accelerate the development of atherosclerotic lesions by aggravating theaccelerate the development of atherosclerotic lesions by aggravating the
basic mechanismbasic mechanism of shear stress, thatof shear stress, that he felt was responsible.he felt was responsible.
 FewFew days after, inspired bydays after, inspired by the findings from the researchers in Californiathe findings from the researchers in California
and by theand by the information brought byinformation brought by Dr. PaulDr. Paul RoschRosch,, II came tocame to the draftthe draft
about the acidity theory of atherosclerosisabout the acidity theory of atherosclerosis..

 GaskettGaskett demonstrated in 1880 that acid solutions havedemonstrated in 1880 that acid solutions have effects oneffects on thethe
contractility of heart tissues and vascular smooth muscle,contractility of heart tissues and vascular smooth muscle, reasoning thatreasoning that
this was one important mechanism for the localthis was one important mechanism for the local regulation ofregulation of blood flowblood flow
during increased metabolicduring increased metabolic activity.activity.
 (Gaskell(Gaskell WH. On the tonicity of the heart and blood vessels. JWH. On the tonicity of the heart and blood vessels. J PhysiolPhysiol 1880;3:481880;3:48--75)75)
 ZsoterZsoter et al have shown in 1961 that reduction of blood pH increases bloodet al have shown in 1961 that reduction of blood pH increases blood
flow.flow.
 ((ZsoterZsoter,, BandemanBandeman L,L, ChappelChappel CL. The effect of local pH changes on blood flow inCL. The effect of local pH changes on blood flow in
the dog. Am Heart J. 1961;61: 777the dog. Am Heart J. 1961;61: 777--782)782)

 In 1977 JamesIn 1977 James P. Henry and Patricia M. Stephens were the first toP. Henry and Patricia M. Stephens were the first to
postulatepostulate that chronic stress or the constantly heightened sympatheticthat chronic stress or the constantly heightened sympathetic--
adrenomedullaryadrenomedullary activity may lead toactivity may lead to atherosclerosisatherosclerosis andand cardiovascularcardiovascular
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
SociobiologicSociobiologic Approach to Medicine. Springer; First edition, Dec 21Approach to Medicine. Springer; First edition, Dec 21 19771977

 SequenceSequence ofof events*events*
 I. Sympathetic dominance by continuous stress plusI. Sympathetic dominance by continuous stress plus
 II. Deficiency in production of endogenous digitalisII. Deficiency in production of endogenous digitalis--likelike compoundscompounds withwith
alterations ofalterations of sodiumsodium--potassium pumppotassium pump activity results inactivity results in
 III. Lowered pH (acidity) that increases perfusion pressure and provokesIII. Lowered pH (acidity) that increases perfusion pressure and provokes
effects on contractility of coronary arteries, leading to changes ineffects on contractility of coronary arteries, leading to changes in
hemodynamic shear stress and atherosclerosis ashemodynamic shear stress and atherosclerosis as consequence.consequence.
 *Carlos*Carlos ETBETB MonteiroMonteiro, Acidic environment evoked by chronic stress: A novel, Acidic environment evoked by chronic stress: A novel
mechanism to explainmechanism to explain atherogenesisatherogenesis. Available from Infarct Combat Project,. Available from Infarct Combat Project,
January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdfJanuary 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

 TheThe heart is an organ of high metabolic activityheart is an organ of high metabolic activity –– that cannot rest as otherthat cannot rest as other
body muscles, being susceptible to drops in pH during ischemia andbody muscles, being susceptible to drops in pH during ischemia and
hypoxia.hypoxia. The chronic or acute elevated catecholamine release, mainlyThe chronic or acute elevated catecholamine release, mainly
from sympathetic nerve terminals in cardiacfrom sympathetic nerve terminals in cardiac tissue, maytissue, may accelerate theaccelerate the
myocardialmyocardial glycolysisglycolysis leading to significant increase in lactate productionleading to significant increase in lactate production..
 TheThe association of increased lipid levels with abnormal lactateassociation of increased lipid levels with abnormal lactate
metabolism may provide a useful screening test for the detection ofmetabolism may provide a useful screening test for the detection of
coronary arterycoronary artery disease, according a study. Other study has demonstrateddisease, according a study. Other study has demonstrated
thatthat plasma lipid abnormalities and myocardial lactate productionplasma lipid abnormalities and myocardial lactate production werewere
significantly associated with subsequentsignificantly associated with subsequent arteriographicarteriographic progression. Theprogression. The
amount of lactate released by the myocardium has been shown to beamount 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.
 InIn our opinion the raise in plasma lipids presented in these studies mightour opinion the raise in plasma lipids presented in these studies might
be a response to injury of the arterial endothelium due to an increasedbe a response to injury of the arterial endothelium due to an increased
release ofrelease 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 ofThe 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 coronaryDiagnosis of coronary artery disease by estimation of coronary
sinus lactate. British Heart Journal, 1978, 40, 979sinus lactate. British Heart Journal, 1978, 40, 979--983983 ; Bemis; Bemis CE,CE, GorlinGorlin R, et al.R, et al.
Progression of coronary artery disease: A clinicalProgression of coronary artery disease: A clinical arteriographicarteriographic study. Circulation,study. Circulation,
VolVol XLVII, MarchXLVII, March 1973)1973)

 TThe sympathetic activation with elevation of circulating catecholaminehe sympathetic activation with elevation of circulating catecholamine
((adrenalineadrenaline, etc..), cause, etc..), cause coronarycoronary vasoconstrictionvasoconstriction andand consequentconsequent
reductionreduction inin bloodblood flowflow..
 On the other hand the increased lactate (or decreased blood pH) may evokeOn the other hand the increased lactate (or decreased blood pH) may evoke
vascular smooth muscle relaxation and increase of bloodvascular smooth muscle relaxation and increase of blood flowflow..
 These opposite forces working in sequenceThese opposite forces working in sequence -- with the sympathetic overdrivewith the sympathetic overdrive
leading to metabolic acidosis, in our view, may be reconciled to partiallyleading to metabolic acidosis, in our view, may be reconciled to partially
explain the occurrence of the resulting abnormal stretching/relaxing ofexplain the occurrence of the resulting abnormal stretching/relaxing of
coronary arteries, in different directions, simultaneously, producing changescoronary 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 AtherosclerosisBook “Acidity Theory of Atherosclerosis –– New Evidences”, 2012New Evidences”, 2012

 Studies suggest that some risk factors for coronary artery disease, likeStudies suggest that some risk factors for coronary artery disease, like
stress (anxiety, hostility,stress (anxiety, hostility, extreme physical exertionextreme physical exertion , etc..), high, etc..), high
carbohydrate diets andcarbohydrate diets and smoke may raisesmoke may raise total cholesterol and low densitytotal cholesterol and low density
lipoproteinslipoproteins levels.levels.
 Also, it is interesting to notice that in stress conditions, high carbohydrateAlso, it is interesting to notice that in stress conditions, high carbohydrate
diets and cigarette smoking there is a significant elevation in blooddiets 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 thecontaining 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 atherosclerosisReferences at the book: Acidity Theory of atherosclerosis –– New Evidences, 2012New Evidences, 2012

In the next slides we will discuss about theIn the next slides we will discuss about the
dysregulationdysregulation of the autonomic nervous system, as theof the autonomic nervous system, as the
underlying mechanism in psychosocial and other riskunderlying mechanism in psychosocial and other risk
factors for atherosclerosis/coronary artery disease thatfactors for atherosclerosis/coronary artery disease that
are related with sympathetic dominance, throughare related with sympathetic dominance, through
sympathetic oversympathetic over--activity or parasympatheticactivity or parasympathetic
withdrawal.withdrawal.

 TheThe 5 specific psychosocial domains5 specific psychosocial domains that contributethat contribute significantly to thesignificantly to the
pathogenesis and expression of coronary arterypathogenesis and expression of coronary artery disease are:disease are:
 Depression;Depression;
 Anxiety;Anxiety;
 PersonalityPersonality factors and characterfactors and character traits;traits;
 Social isolationSocial isolation;;
 ChronicChronic life stress.life stress.
 (Alan(Alan RozanskiRozanski, 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 forFactors on the Pathogenesis of Cardiovascular Disease and Implications for
Therapy. Circulation. 1999;99:2192Therapy. Circulation. 1999;99:2192--2217;2217; VeithVeith RC et al. SympatheticRC et al. Sympathetic nervousnervous
system activity in major depression. Basal andsystem activity in major depression. Basal and desipraminedesipramine--induced alterations ininduced alterations in
plasma norepinephrine kinetics.plasma norepinephrine kinetics. ArchArch Gen Psychiatry. 1994 May;51(5):Gen Psychiatry. 1994 May;51(5):411411--22)22)

AtherosclerosisAtherosclerosis and age are intimately linked, being the best example of anand age are intimately linked, being the best example of an
ageage--related disease.related disease. ItIt isis generallygenerally acceptedaccepted that sympathetic nervous activitythat sympathetic nervous activity
increases progressively with age. Also that plasma noradrenaline levelsincreases progressively with age. Also that plasma noradrenaline levels
increase may be mediated by the age related impairment ofincrease may be mediated by the age related impairment of baroreflexbaroreflex
sensitivitysensitivity..
(Ziegler MG, Lake CR and(Ziegler MG, Lake CR and KopinKopin IJ. Plasma noradrenaline increases with age. NatureIJ. Plasma noradrenaline increases with age. Nature
261, 33261, 33 --335 (27 May 1976); Shimada and all. Age335 (27 May 1976); Shimada and all. Age--related changes ofrelated changes of baroreflexbaroreflex function,function,
plasma norepinephrine , and blood pressure. Hypertension 7:113plasma norepinephrine , and blood pressure. Hypertension 7:113--117, 1985;117, 1985; NarkiewiczNarkiewicz
et al. Genderet al. Gender--selective interaction between aging, blood pressure and sympatheticselective interaction between aging, blood pressure and sympathetic
nerve activity. Hypertension 2005;45:522nerve activity. Hypertension 2005;45:522--525)525)

 AA recent study have demonstrated that sympathetic predominance mayrecent study have demonstrated that sympathetic predominance may
favor the development of sustained hypertension andfavor the development of sustained hypertension and
hypercholesterolemia early in life, and lead to increased susceptibility tohypercholesterolemia early in life, and lead to increased susceptibility to
vascular complications.vascular complications.
 ((PalatiniPalatini PP, et al., et al. EvolutionEvolution ofof bloodblood pressurepressure andand cholesterolcholesterol inin stagestage 11
hypertensionhypertension: role: role ofof autonomicautonomic nervousnervous systemsystem activityactivity.. JournalJournal ofof
HypertensionHypertension 2006,2006, 24:137524:1375--1381)1381)

 HypertensionHypertension is considered as an important risk factor for theis considered as an important risk factor for the
development of atherosclerosis, with these processes sharing somedevelopment of atherosclerosis, with these processes sharing some
common mechanisms. The endothelium is usually placed as the probablecommon mechanisms. The endothelium is usually placed as the probable
central focus for the effects in both diseases, with evidences leading to thecentral 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 ofThe sympathetic activation plays an important role in the regulation of
the bloodthe blood pressure.pressure.
 ((GrassiGrassi G,G, SeravalleSeravalle G et al. Sympathetic andG et al. Sympathetic and baroreflexbaroreflex cardiovascular control incardiovascular control in
hypertensionhypertension--related left ventricular dysfunction. Hypertensionrelated left ventricular dysfunction. Hypertension 2009;53:2052009;53:205--209 ;209 ;
GrassiGrassi G,G, BertoliBertoli S,S, SeravalleSeravalle G. Sympathetic nervous system: role in hypertensionG. Sympathetic nervous system: role in hypertension
and in chronic kidney disease.and in chronic kidney disease. CurrCurr OpinOpin NephrolNephrol HypertensHypertens, 2010, Nov, 2010, Nov 10; Joyner10; Joyner
MJ,MJ, CharkoudianCharkoudian N andN and WallinWallin BG. Sympathetic nervous system and bloodBG. 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; 56:1056:10--16)16)

 PatientsPatients with chronic kidney disease are at increased risk ofwith chronic kidney disease are at increased risk of
atherosclerotic cardiovascular disease.atherosclerotic cardiovascular disease.
 A marked increase in sympathetic neural discharge, as assessed via theA marked increase in sympathetic neural discharge, as assessed via the
microneurographicmicroneurographic technique, has been shown to occur in thetechnique, has been shown to occur in the predialyticpredialytic
stage of chronic renal failure. Recent evidence, however, indicates thatstage of chronic renal failure. Recent evidence, however, indicates that
also in the earlier clinical phases of kidney disease, sympathetic activationalso in the earlier clinical phases of kidney disease, sympathetic activation
is detectable. Further data show that sympathetic neural mechanismsis detectable. Further data show that sympathetic neural mechanisms
participate in renal and/or hypertensive disease progression,participate in renal and/or hypertensive disease progression, favoringfavoring thethe
development of target organ damage.development of target organ damage.
 ((GrassiGrassi G,G, BertolliBertolli S,S, SeravalleSeravalle G. Sympathetic nervous system: role in hypertensionG. Sympathetic nervous system: role in hypertension
and in chronic kidney disease.and in chronic kidney disease. CurrCurr OpinOpin NephrolNephrol HypertensHypertens 2012 Jan;21(1):462012 Jan;21(1):46--5151.).)

 PatientsPatients with diabetes are at increased risk forwith diabetes are at increased risk for atherosclerosis.atherosclerosis. It has longIt has long
been recognized that cardiac autonomic neuropathy increases morbiditybeen recognized that cardiac autonomic neuropathy increases morbidity
and mortality in diabetes and may have greater predictive power thanand mortality in diabetes and may have greater predictive power than
traditional risk factors for cardiovascular events. Significant morbiditytraditional risk factors for cardiovascular events. Significant morbidity
and mortalityand mortality in diabetes canin diabetes can now be attributable to autonomic imbalancenow be attributable to autonomic imbalance
between the sympathetic and parasympathetic nervous system regulationbetween the sympathetic and parasympathetic nervous system regulation
ofof cardiovascular function.cardiovascular function.
 (Beckman(Beckman JA,CreagerJA,Creager MA, Libby P. Diabetes and Atherosclerosis. JAMA. 2002;MA, Libby P. Diabetes and Atherosclerosis. JAMA. 2002;
287(19):287(19):25702570--2581;2581; VinikVinik AI,AI, ZieglertZieglert D. Autonomic imbalance: prophet of doom orD. Autonomic imbalance: prophet of doom or
scope for hope?scope for hope? DiabetDiabet. Med. 28, 643. Med. 28, 643--651 (2011)651 (2011)

 CigaretteCigarette smoking increases efferent sympathetic nerve traffic acutely, assmoking increases efferent sympathetic nerve traffic acutely, as
well norepinephrine and epinephrine releasewell norepinephrine and epinephrine release.. The acuteThe acute
sympathoexcitatorysympathoexcitatory effects of smoking on the cardiovascular system areeffects of smoking on the cardiovascular system are
partially mediated by catecholamine release, muscle sympathetic nervepartially mediated by catecholamine release, muscle sympathetic nerve
excitation and peripheral chemoreceptor sensitivity increase, consecutiveexcitation and peripheral chemoreceptor sensitivity increase, consecutive
to nicotinic receptor stimulation in the autonomic nervousto nicotinic receptor stimulation in the autonomic nervous system. Bothsystem. Both
active smoking and exposure toactive smoking and exposure to environmentalenvironmental tobacco smoke aretobacco smoke are
associated with the progression of atherosclerosis as indexed by intimalassociated with the progression of atherosclerosis as indexed by intimal--
medial thickness of the carotid artery assessed bymedial thickness of the carotid artery assessed by ultrasoundultrasound. Carotid. Carotid
intimaintima--mediamedia thickness isthickness is a valid surrogate measure for coronarya valid surrogate measure for coronary
atherosclerosis.atherosclerosis.
 Blood lactate levels are increased after passive smoking.Blood lactate levels are increased after passive smoking.
 ((NiedermaierNiedermaier ON, Smith ML.ON, Smith ML. Influence of cigarette smoking on human autonomicInfluence of cigarette smoking on human autonomic
function. Circulation 1993, 88:562function. Circulation 1993, 88:562--571571 ;; AdamopoulusAdamopoulus D, van de Borne P andD, van de Borne P and
ArgachaArgacha JF, New insights into the sympathetic, endothelial and coronary effects ofJF, New insights into the sympathetic, endothelial and coronary effects of
nicotine.nicotine. ClinClin ExpExp PharmacolPharmacol PhysiolPhysiol 2008; 35(4):2008; 35(4): 458458--63; Howard63; Howard G et al, CigaretteG et al, Cigarette
smoking and progression of atherosclerosis: The Atherosclerosis Risk insmoking and progression of atherosclerosis: The Atherosclerosis Risk in
Communities (ARIC) Study. JAMA, 1998 Jan 14;279(2):119Communities (ARIC) Study. JAMA, 1998 Jan 14;279(2):119--24.24. YarliogluesYarlioglues M.M. KayaKaya
MG et al. DoseMG et al. Dose--dependent acute effects of passive smoking on left ventriculardependent acute effects of passive smoking on left ventricular
cardiac function in health volunteers. Jcardiac function in health volunteers. J InvestigInvestig Med 2012 , Feb; 60 (2): 517Med 2012 , Feb; 60 (2): 517--22)22)

 AA recentrecent studystudy inin humanshumans havehave confirmedconfirmed thethe associationassociation ofof thethe exposureexposure
toto ambientambient airair pollutionpollution andand atherosclerosisatherosclerosis,, throughthrough thethe progressionprogression ofof
carotidcarotid arteryartery intimaintima--mediamedia thicknessthickness .. AlsoAlso, some, some investigatorsinvestigators havehave
demonstrateddemonstrated thatthat particulateparticulate airair pollutantspollutants continuouscontinuous expositionexposition
decreasesdecreases thethe heartheart raterate variabilityvariability andand may lead tomay lead to anan impairedimpaired
autonomicautonomic controlcontrol withwith potentialpotential accelerationacceleration inin thethe progressionprogression ofof
atherosclerosisatherosclerosis..
 (Nino(Nino KunzliKunzli et al.et al. ""AmbientAmbient AirAir PollutionPollution andand thethe ProgressionProgression ofof AtherosclerosisAtherosclerosis
inin AdultsAdults."." PloSPloS ONE 5(2):ONE 5(2): e9096,e9096, FebruaryFebruary 8,8, 2010;2010; DuanpingDuanping LiaoLiao et al.et al.
AssociationAssociation ofof HigherHigher LevelsLevels ofof AmbientAmbient CriteriaCriteria PollutantsPollutants withwith ImpairedImpaired CardiacCardiac
AutonomicAutonomic ControlControl: A: A PopulationPopulation--basedbased StudyStudy,, AmAm JJ EpidemiolEpidemiol 2004;159:7682004;159:768––777;777;
C.C. ArdenArden PopePope III et al.III et al. AmbientAmbient ParticulateParticulate AirAir PollutionPollution, Heart Rate, Heart Rate VariabilityVariability,,
andand BloodBlood MarkersMarkers ofof InflammationInflammation in ain a PanelPanel ofof ElderlyElderly SubjectsSubjects. Environmental. Environmental
Health Perspectives, V 112; N 3:Health Perspectives, V 112; N 3: MarchMarch 2004;2004; HeikkiHeikki V et al.V et al. Heart RateHeart Rate VariabilityVariability
andand ProgressionProgression ofof CoronaryCoronary AtherosclerosisAtherosclerosis.. ArteriosclerosisArteriosclerosis,, ThrombosisThrombosis,, andand
VascularVascular BiologyBiology.. 1999;19:19791999;19:1979--1985)1985)

 Road traffic and aircraft noise near airports causes stress reactions similarRoad traffic and aircraft noise near airports causes stress reactions similar
to other stressors in the occupational and ambient environment. In theseto other stressors in the occupational and ambient environment. In these
situations of sympathetic and endocrine arousal, concentrations of stresssituations of sympathetic and endocrine arousal, concentrations of stress
hormones in the blood are increased. Laboratory and epidemiologicalhormones in the blood are increased. Laboratory and epidemiological
studies have demonstrated a link between noise and cardiovascularstudies have demonstrated a link between noise and cardiovascular
disease.disease.
 ((BabischBabisch 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;5:1Noise Health 2003;5:1--11;11; BabischBabisch W. Transportation noise and cardiovascularW. Transportation noise and cardiovascular
risk: updated review and synthesis of epidemiological studies indicate that therisk: updated review and synthesis of epidemiological studies indicate that the
evidence has increased. Noise Health 2006;8:1evidence has increased. Noise Health 2006;8:1––29; Eriksson C,29; Eriksson C, RosenlundRosenlund M,M,
PershagenPershagen G,G, HildingHilding A,A, OstensonOstenson C,C, BluhmBluhm G. Aircraft noise and incidence ofG. Aircraft noise and incidence of
hypertension. Epidemiology 2007;18:716hypertension. Epidemiology 2007;18:716––721;721; JarupJarup L,L, BabischBabisch W,W, HouthuijsHouthuijs D,D,
PershagenPershagen G,G, KatsouyanniKatsouyanni K,K, CadumCadum E, Dudley M,E, Dudley M, SavignySavigny P,P, SeiffertSeiffert 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 HealthEnviron Health PerspectPerspect 2008;116:3292008;116:329––333)333)

 ItIt is well established that theis well established that the sympathetic nervous systemsympathetic nervous system activity is alsoactivity is also
influenced by food ingestion, and that diet composition plays aninfluenced by food ingestion, and that diet composition plays an
important role.important role. HighHigh carbohydrate diets, particularly in the form of highcarbohydrate diets, particularly in the form of high--
glycemicglycemic carbohydratecarbohydrate, have the ability to directly induce endothelial, have the ability to directly induce endothelial
dysfunction, vascular inflammation and subsequent development ofdysfunction, vascular inflammation and subsequent development of
atherosclerosis.atherosclerosis. A study from 2009 defendsA study from 2009 defends that thethat the widespread use ofwidespread use of
starchy food and sugars has brought about a new metabolic problem: astarchy food and sugars has brought about a new metabolic problem: a
chronicallychronically increasedincreased sympathetic nervous system activity,sympathetic nervous system activity, where thewhere the
highhigh--glycemic index nutrition has been suggested to play a key role in theglycemic index nutrition has been suggested to play a key role in the
pathogenesis of hypertension andpathogenesis of hypertension and atherosclerosis. Onatherosclerosis. On the other sidethe other side
protein or fat ingestion have no significantprotein or fat ingestion have no significant sympathoexcitatorysympathoexcitatory effect.effect.
(Koop(Koop W. TheW. The atherogenicatherogenic potential of dietary carbohydrate. Preventive Medicine 42potential of dietary carbohydrate. Preventive Medicine 42
(2006):(2006): 336336--342; Koop342; Koop W. Chronically increased activity of the sympathetic nervousW. Chronically increased activity of the sympathetic nervous
system: our dietsystem: 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; WelleWelle 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 fatIncreased plasma norepinephrine levels following glucose but not protein or fat
consumption. Metabolism 1981; 30:consumption. Metabolism 1981; 30: 953953--958;958; TentolourisTentolouris et al. Differential effect ofet al. Differential effect of
highhigh--fat and high carbohydratefat and high carbohydrate isoenergeticisoenergetic meals on cardiac autonomic nervousmeals on cardiac autonomic nervous
system activitysystem activity in leanin lean and obese women. Metabolism 2003; 52:and obese women. Metabolism 2003; 52: 14261426--32)32)

 TheThe prevalence of coronary arteryprevalence of coronary artery diseasedisease is 3 to 5 times higher in patientsis 3 to 5 times higher in patients
withwith obstructive seep apnea (OSA)obstructive seep apnea (OSA) compared with controlcompared with control populations.populations.
Increased carotid intimaIncreased carotid intima--mediamedia thicknessthickness and plaque occurrence wasand plaque occurrence was
reported in OSA patients without any other significant coreported in OSA patients without any other significant co--morbiditymorbidity
compared to matchedcompared to matched controls.controls. OSA patients experience intermittentOSA patients experience intermittent
hypoxaemiahypoxaemia and CO2 retention that modify the autonomic andand CO2 retention that modify the autonomic and
haemodynamichaemodynamic responses toresponses to sleep.sleep. Chronic intermittent hypoxia mayChronic intermittent hypoxia may
lead to sympatheticlead to sympathetic overactivityoveractivity..
 (Marin(Marin JM,JM, CarrizoCarrizo SJ, Vicente E,SJ, Vicente E, AgustiAgusti AG.AG. LongLong--termterm cardiovascularcardiovascular outcomesoutcomes
inin menmen withwith obstructiveobstructive sleepsleep apnoeaapnoea––hypopnoeahypopnoea withwith oror withoutwithout treatmenttreatment withwith
continuouscontinuous positivepositive airwayairway pressurepressure:: anan observationalobservational studystudy. Lancet 2005; 365:. Lancet 2005; 365:
10461046––1053;1053; SomersSomers VK,VK, DykenDyken ME, Mark AL,ME, Mark AL, AbboudAbboud FM.FM. SympatheticSympathetic nervenerve
activityactivity duringduring sleepsleep in normalin normal subjectssubjects. N. N EnglEngl JJ MedMed 1993; 328 :1993; 328 : 303303--7;7; Johnson, T.Johnson, T.
SS.. andand allall.. Greenberg HE,Greenberg HE, andand allall.. ChronicChronic intermittentintermittent hypoxiahypoxia increasesincreases
sympatheticsympathetic responsivenessresponsiveness toto hypoxiahypoxia andand hypercapniahypercapnia. J. J ApplAppl PhysiolPhysiol 1999; 86:1999; 86:
298298––305)305)

 SomeSome recent studies have demonstrated that coronary atherosclerosis isrecent studies have demonstrated that coronary atherosclerosis is
more severe in patients with vascularmore severe in patients with vascular erectile dysfunction (ED),erectile dysfunction (ED), withwith
indicationsindications that ED may be an additional, early warning sign of coronarythat ED may be an additional, early warning sign of coronary
atherosclerosis. One of theseatherosclerosis. One of these has shown that men with idiopathic ED havehas 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. Tincreased pulse pressure and impaired heart rate variability. Thehe authorsauthors
say thissay this support the concept that erectile dysfunction is a predictor ofsupport the concept that erectile dysfunction is a predictor of
cardiovascular dysfunction and a precursor of clinical cardiovascularcardiovascular dysfunction and a precursor of clinical cardiovascular
disease.disease. A very recent study has demonstrated that patients with EDA 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 EDconfirming the results of other studies showing that patients with ED
may have excessive sympatheticmay have excessive sympathetic activity.activity.
 ((ChiurliaChiurlia E et al. Subclinical coronary artery atherosclerosis in patients with erectileE et al. Subclinical coronary artery atherosclerosis in patients with erectile
dysfunction. J Amdysfunction. J Am CollColl CardiolCardiol, 2005;, 2005; 46:150346:1503--63; Stuckey63; Stuckey BG, Walsh JPBG, Walsh JP et al.et al.
Erectile dysfunction predictsErectile dysfunction predicts generalisedgeneralised cardiovascular disease. Evidence from acardiovascular disease. Evidence from a
case control study. Atherosclerosis 2007, 194(2):case control study. Atherosclerosis 2007, 194(2):458458--64; Lee64; Lee JYJY etet al. Heart rateal. Heart rate
variability in men with erectile dysfunction.variability in men with erectile dysfunction. IntInt NeurourolNeurourol JJ 2011;15:872011;15:87--91)91)

 TheThe metabolic syndrome is associated with increased risk formetabolic syndrome is associated with increased risk for
development of both cardiovascular disease and typedevelopment of both cardiovascular disease and type--2 diabetes in2 diabetes in
humans. Central obesity and insulin resistance are thought to representhumans. Central obesity and insulin resistance are thought to represent
common underlying factors of the syndrome, which features a chroniccommon underlying factors of the syndrome, which features a chronic
lowlow--grade inflammatory stategrade inflammatory state .. Several markers of adrenergic drive, suchSeveral markers of adrenergic drive, such
as plasma norepinephrine, norepinephrine spillover from adrenergicas plasma norepinephrine, norepinephrine spillover from adrenergic
nerve terminals, heart rate and others, with sympathetic activation, havenerve terminals, heart rate and others, with sympathetic activation, have
all shown an increase in the different conditions clustering in metabolicall shown an increase in the different conditions clustering in metabolic
syndrome like obesity, hypertension and insulin resistancesyndrome like obesity, hypertension and insulin resistance state.state.
 ((PaolettiPaoletti R,R, BolegoBolego C, Poli A,C, Poli A, andand CignarellaCignarella A.A. MetabolicMetabolic SyndromeSyndrome,, InflammationInflammation
andand AtherosclerosisAtherosclerosis.. VascVasc HealthHealth RiskRisk ManagManag. 2006. 2006 JuneJune; 2(2):; 2(2): 145145––152;152; ManciaMancia G,G,
BousquetBousquet P et al. TheP et al. The sympatheticsympathetic nervousnervous systemsystem andand thethe metabolicmetabolic syndromesyndrome..
JournalJournal ofof HypertensionHypertension 2007, 25 (5):2007, 25 (5):909909--920; Grassi920; Grassi G,G, QuartiQuarti--TrevanoTrevano F et al.F et al.
CardiovascularCardiovascular riskrisk andand adrenergicadrenergic overdriveoverdrive inin metabolicmetabolic syndromesyndrome.. NutrNutr MetabMetab
CardiovascCardiovasc DisDis 2007, 17(6):2007, 17(6): 473473--81)81)

 PeriodontalPeriodontal 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 infectionmay represent a favorable scenario to verify the connection of infection
and atherosclerosis/cardiovascularand atherosclerosis/cardiovascular disease. Severaldisease. Several studies arestudies are
suggesting an oral source for atherosclerotic plaquesuggesting an oral source for atherosclerotic plaque -- associated bacteriaassociated bacteria
with demonstration about the presence of viable periodontal pathogenswith demonstration about the presence of viable periodontal pathogens
in atheroscleroticin atherosclerotic plaques.plaques. In this regard an interesting hypothesis wasIn this regard an interesting hypothesis was
proposed in 2004 that periodontal infection may lead to brief episodes ofproposed in 2004 that periodontal infection may lead to brief episodes of
bacteremia with inoculation of atherosclerotic plaque by periodontalbacteremia with inoculation of atherosclerotic plaque by periodontal
pathogenspathogens. However, important information is left aside by most. However, important information is left aside by most
investigators studying the connection between oral infection andinvestigators studying the connection between oral infection and
atherosclerosis/coronary myocardialatherosclerosis/coronary myocardial disease. These investigators don’tdisease. These investigators don’t
take in consideration that the sympathetic nervous system is intenselytake in consideration that the sympathetic nervous system is intensely
activated during bacteremia.activated during bacteremia.
((GaettiGaetti--Jardim E et al.Jardim E et al. QuantitativeQuantitative detectiondetection ofof periodontopathicperiodontopathic bacteriabacteria inin
atheroscleroticatherosclerotic plaquesplaques fromfrom coronarycoronary arteriesarteries. J. J MedMed MicrobiolMicrobiol 58:156858:1568––1575, 20091575, 2009;;
LeinhardtLeinhardt DJ et al.DJ et al. Plasma NEPlasma NE concentrationsconcentrations dodo notnot accuratelyaccurately reflectreflect sympatheticsympathetic
nervousnervous systemsystem activityactivity inin humanhuman sepsissepsis.. AmAm JJ PhysiolPhysiol 1993;1993; 265:E2848;265:E2848; StraubStraub RH et al.RH et al.
AblationAblation ofof thethe sympatheticsympathetic nervousnervous systemsystem decreasesdecreases gramgram--negativenegative andand increasesincreases
gramgram--positivepositive bacterialbacterial disseminationdissemination:: keykey roles for tumorroles for tumor necrosisnecrosis factorfactor//phagocytesphagocytes
andand interleukininterleukin--4/4/lymphocyteslymphocytes.. InfectInfect DisDis. 2005. 2005 AugAug 15;192(4):15;192(4):560560--72)72)

 ThereThere isis anan intenseintense discussiondiscussion onon thethe benefitsbenefits andand potentialpotential harmharm ofof
reducingreducing saltsalt intakeintake inin thethe generalgeneral populationpopulation. In. In ourour viewview,, bothboth
restrictionrestriction andand highhigh saltsalt intakeintake maymay resultresult inin coronarycoronary arteryartery diseasedisease*. The*. The
reasonreason isis thatthat inin bothboth casescases existsexists anan increasedincreased sympatheticsympathetic nervenerve activityactivity..
 (*Book “Acidity theory of atherosclerosis(*Book “Acidity theory of atherosclerosis –– New Evidences”, by CarlosNew Evidences”, by Carlos MonteiroMonteiro..
Chapter: ‘BothChapter: ‘Both restriction and high salt intake may result in cardiovascularrestriction and high salt intake may result in cardiovascular
disease’, 2012, Amazon.com;disease’, 2012, Amazon.com; StolarzStolarz--SkrypekSkrypek K, et al. Fatal and nonfatal outcomes,K, et al. Fatal and nonfatal outcomes,
incidence ofincidence of hypertensionhypertension, and blood pressure changes in relation to urinary, and blood pressure changes in relation to urinary
sodium excretion. JAMA 2011;sodium excretion. JAMA 2011; 305:1777305:1777--1785; Guido1785; Guido GrassiGrassi, et al. Short, et al. Short-- and Longand Long--
TermTerm NeuroadrenergicNeuroadrenergic Effects of Moderate Dietary Sodium restriction in EssentialEffects of Moderate Dietary Sodium restriction in Essential
Hypertension. Circulation. 2002;106: 1957Hypertension. Circulation. 2002;106: 1957--1961;1961; 'Volume'Volume--expandedexpanded' hypertension:' hypertension:
the effect of fluid overload and the role of the sympathetic nervous system in saltthe effect of fluid overload and the role of the sympathetic nervous system in salt--
dependent hypertension, Journal of Hypertension, V30; N1: Januarydependent hypertension, Journal of Hypertension, V30; N1: January 2012)2012)

 Insomnia is characterized by a constant sympathetic hyperInsomnia is characterized by a constant sympathetic hyper--activation.activation.
 In 1999 was hypothesized that insomnia may be related to continualIn 1999 was hypothesized that insomnia may be related to continual
stressors, reduced slowstressors, reduced slow--wave sleep, and autonomic dysfunction, whichwave sleep, and autonomic dysfunction, which
increase the risk of heart problems.increase the risk of heart problems.
 (de(de ZambottiZambotti M,M, CovassinCovassin N,N, SarloSarlo M, DeM, De MinMin Tona G,Tona G, TrinderTrinder J,J, StegagnoStegagno L.L.
Nighttime cardiac sympathetic hyperNighttime cardiac sympathetic hyper--activation in young primary insomniacs.activation in young primary insomniacs.
ClinClin AutonAuton ResRes.. 2013 Feb;23(1):492013 Feb;23(1):49--56; Schwartz S, McDowell Anderson W, Cole56; Schwartz S, McDowell Anderson W, Cole
SR,SR, CornoniCornoni--Huntley J, Hays JC, Blazer D. Insomnia and heart disease: a review ofHuntley J, Hays JC, Blazer D. Insomnia and heart disease: a review of
epidemiologic studies. Jepidemiologic studies. J PsychosomPsychosom Res. 1999 Oct;47(4):313Res. 1999 Oct;47(4):313--33;)33;)

 Studies have shown that longStudies have shown that long--term marathon runners may haveterm marathon runners may have
increased coronary calcium and calcified plaque volume. Other studiesincreased coronary calcium and calcified plaque volume. Other studies
support an increased awareness of atherosclerosis prevalence andsupport 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 bloodIn our view the sympathetic activation and the resulted increase in blood
lactate levels may represent the biological mechanism leading tolactate levels may represent the biological mechanism leading to
atherosclerosis in marathon runnersatherosclerosis in marathon runners.
 (Schwartz JG, Merkel(Schwartz JG, Merkel--Kraus S, Duval S, et al. Does elite athleticism enhance orKraus S, Duval S, et al. Does elite athleticism enhance or
inhibit coronary artery plaque formation.inhibit coronary artery plaque formation. AmericanAmerican CollegeCollege ofof CardiologyCardiology 20102010
ScientificScientific SessionsSessions;; MarchMarch 16, 2010; Atlanta, GA;16, 2010; Atlanta, GA; Kroger K et al. Carotid andKroger K et al. Carotid and
peripheral atherosclerosis in male marathon runners. Medperipheral atherosclerosis in male marathon runners. Med SciSci SportsSports ExercExerc.. 20112011
Jul;43(7):1142Jul;43(7):1142--7;7; Beth A TaylorBeth A Taylor etet al.al. Influence of chronic exercise on carotidInfluence of chronic exercise on carotid
atherosclerosis in marathon runners,atherosclerosis in marathon runners, BMJ Open 2014;4:e004498)BMJ Open 2014;4:e004498)

 AA historyhistory ofof preeclampsiapreeclampsia havehave aa higherhigher riskrisk ofof cardiovascularcardiovascular diseasedisease andand
mortalitymortality inin laterlater lifelife.. StudiesStudies havehave shownshown thatthat womenwomen withwith preeclampsiapreeclampsia hadhad
significantlysignificantly moremore atherosclerosticatherosclerostic plaquesplaques thanthan parousparous controlscontrols.. TheThe carotidcarotid
intimaintima--mediamedia thicknessthickness inin thesethese womenwomen withwith prepre--eclampsiaeclampsia alsoalso tendedtended toto bebe
higherhigher thanthan inin otherother groupsgroups..
 TheThe autonomicautonomic nervousnervous systemsystem appearsappears to playto play anan importantimportant role inrole in thethe etiologyetiology ofof
preeclampsiapreeclampsia wherewhere therethere isis increased sympathetic and decreasedincreased sympathetic and decreased
parasympathetic control of heart rateparasympathetic control of heart rate.. TheThe lactatelactate dehydrogenasedehydrogenase levelslevels areare alsoalso
significantlysignificantly elevatedelevated inin womenwomen withwith preeclampsiapreeclampsia..
 ((HaukkamaaHaukkamaa L,L, MoilanenMoilanen L,L, KattainenKattainen A,A, LuotoLuoto R et al. 2009. PreR et al. 2009. Pre--eclampsiaeclampsia is a risk factor ofis a risk factor of
carotid artery atherosclerosis.carotid artery atherosclerosis. CerebrovascCerebrovasc DisDis 27(6): 59927(6): 599--607;607; BlaauwBlaauw J, vanJ, van PampusPampus MG,MG,
DoormalDoormal JV, et al. 2006. IncreasedJV, et al. 2006. Increased intimaintima--mediamedia--thickness after early onset of preeclampsia.thickness after early onset of preeclampsia.
ObstetObstet GynecolGynecol 107(6): 1345107(6): 1345--51. N.51. N. SharashkinaSharashkina etet al.al. Preeclampsia and pregnancy inducedPreeclampsia and pregnancy induced
hypertension and carotid artery atherosclerosis. Pregnancy Hypertension 2012,V2; I3: 294hypertension and carotid artery atherosclerosis. Pregnancy Hypertension 2012,V2; I3: 294--295;295;
Yang, Cheryl C. H., TeYang, Cheryl C. H., Te--Chang Chao et al.Chang Chao et al. PreeclampticPreeclamptic pregnancy is associated withpregnancy is associated with
increased sympathetic and decreased parasympathetic control of HR. Am Jincreased sympathetic and decreased parasympathetic control of HR. Am J PhysiolPhysiol Heart CircHeart Circ
PhysiolPhysiol 2000,2000, 278: 1269278: 1269––1273;1273; He S,He S, BremmeBremme K,K, KallnerKallner A, et al. Increased concentrations ofA, et al. Increased concentrations of
lactatelactate dehydrogenasedehydrogenase in pregnancy with preeclampsia; a predictor for birth of small forin pregnancy with preeclampsia; a predictor for birth of small for
gestational age infants.gestational age infants. GynecolGynecol ObstetObstet Invest. 1995;39:234Invest. 1995;39:234––8;8; Catanzerite VA, Steinberg SM,Catanzerite VA, Steinberg SM,
Mosley CA, et al. SevereMosley CA, et al. Severe preeclampsia withpreeclampsia with fulminantfulminant and extreme elevation ofand extreme elevation of aspartateaspartate
aminotransferaseaminotransferase andand lactatelactate dehydrogenasedehydrogenase levelslevels.. AmAm JJ PerinatolPerinatol. 1995;12:310. 1995;12:310––3)3)

 HyperhomocysteinemiaHyperhomocysteinemia has been reported to be associated with bothhas 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 relationshipSome studies have shown a relationship betweenbetween homocysteinehomocysteine andand
psychological risk factors for cardiovascular diseases, like hostility andpsychological risk factors for cardiovascular diseases, like hostility and
anger. However, a subsequent study revealed that thereanger. However, a subsequent study revealed that there is no evidenceis no evidence
for an association betweenfor an association between homocysteinehomocysteine levels and cardiovascularlevels and cardiovascular
autonomic function in either diabetic orautonomic function in either diabetic or nondiabeticnondiabetic subjects.subjects. So,So,
according this later study the cardiovascularaccording this later study the cardiovascular autonomic dysfunction doesautonomic dysfunction does
not helpnot help to explainto explain whywhy hyperhomocysteinaemiahyperhomocysteinaemia is related tois related to
cardiovascular mortalitycardiovascular mortality..
 My take on the biological mechanism is thatMy take on the biological mechanism is that homocysteinehomocysteine and its acidicand its acidic
derivatives might contribute to the acidic coronary blood flow that leadderivatives might contribute to the acidic coronary blood flow that lead toto
increasedincreased perfusion pressureperfusion pressure andand effects on contractility of coronaryeffects on contractility of coronary
arteries,arteries, resulting inresulting in changes in hemodynamic shear stresschanges in hemodynamic shear stress that ends inthat ends in
atherosclerosis/coronary myocardial disease.atherosclerosis/coronary myocardial disease.
 ((StoneyStoney CM,CM, EngebretsonEngebretson TO.TO. PlasmaPlasma homocysteinehomocysteine concentrations are positivelyconcentrations are positively
associated with hostility and anger. Life Sci. 2000;66(23):associated with hostility and anger. Life Sci. 2000;66(23):22672267--7575;; SpoelstraSpoelstra--De ManDe Man
AM,AM, SmuldersSmulders YM et al.YM et al. HomocysteineHomocysteine levels are not associated withlevels are not associated with
cardiovascular autonomic function in elderly Caucasian subjects without or withcardiovascular autonomic function in elderly Caucasian subjects without or with
type 2 diabetes mellitus: the Hoorn Studytype 2 diabetes mellitus: the Hoorn Study.. J Intern Med. 2005 Dec;258(6):536J Intern Med. 2005 Dec;258(6):536--4343.).)

 TheThe studiesstudies associatingassociating cardiovascularcardiovascular diseasedisease withwith thethe expositionexposition toto
certaincertain chemicalschemicals likelike perfluorooctanoicperfluorooctanoic acidacid ,, arsenicarsenic, lead, lead andand cadmiumcadmium
besides some persistent organic pollutants,besides some persistent organic pollutants, remindsreminds meme thethe experimentsexperiments
fromfrom thethe beginningbeginning ofof thethe lastlast centurycentury showingshowing thatthat acidacid--fedfed rabbitsrabbits andand
dogsdogs developdevelop atheroscleroticatherosclerotic lesionslesions. In. In ourour opinionopinion thethe effectseffects generatinggenerating
atheroscleroticatherosclerotic lesionslesions inin thesethese experimentsexperiments werewere causedcaused notnot onlyonly byby
chronicchronic hyperacidityhyperacidity inin rabbitsrabbits andand dogsdogs butbut alsoalso relatedrelated toto anan intenseintense
activationactivation ofof thethe sympatheticsympathetic systemsystem provokedprovoked byby acidacid ingestioningestion..
 ((ShankarShankar A,A, XiaoXiao J,J, DucatmanDucatman A.A. PerfluorooctanoicPerfluorooctanoic AcidAcid andand CardiovascularCardiovascular DiseaseDisease inin
USUS AdultsAdults.. ArchivesArchives ofof InternalInternal Medicine, 2012;Medicine, 2012; HsiehHsieh YC,YC, LienLien LM et al.LM et al. SignificantlySignificantly
increasedincreased riskrisk ofof carotidcarotid atherosclerosisatherosclerosis withwith arsenicarsenic exposureexposure andand polymorphismspolymorphisms inin
arsenicarsenic metabolismmetabolism genes.genes. EnvironEnviron Res. 2011 Aug;111(6):Res. 2011 Aug;111(6):804804--10;10; RevisRevis NW,NW, ZinsmeisterZinsmeister
AR, Bull R. Atherosclerosis and hypertension induction by lead and cadmium ions: anAR, Bull R. Atherosclerosis and hypertension induction by lead and cadmium ions: an
effect prevented by calcium ion. Proceffect prevented by calcium ion. Proc NatlNatl AcadAcad SciSci USA 1981; 78 : 6494USA 1981; 78 : 6494--8;8; MessnerMessner B,B,
KnoflachKnoflach M,M, SeubertSeubert A,A, RitschRitsch A,A, PfallerPfaller K, Henderson B, et al. Cadmium is a novel andK, 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.
ArteriosclerArterioscler ThrombThromb VascVasc BiolBiol 2009;2009; 29:29: 13921392 –– 1398; P. Monica Lind, Bert van1398; P. Monica Lind, Bert van BavelBavel,,
SamiraSamira SalihovicSalihovic and Lars Lind. Circulating Levels of Persistent Organic Pollutantsand 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 PerspectPerspect 120:38120:38––4343
(2012);(2012); LoebLoeb, O.,, O., UeberUeber experimentelleexperimentelle ArterienveraenderArterienveraender ungenungen mitmit besondererbesonderer
BeruecksichtigungBeruecksichtigung derder WirkungWirkung derder MilchsaeureMilchsaeure aufauf GrundGrund eigenereigener VersucheVersuche,, DeutschDeutsch..
med.med. WchnschrWchnschr., I913,., I913, xxxixxxxix, I819; I. Adler, ‘, I819; I. Adler, ‘StudiesStudies in Experimentalin Experimental atherosclerosisatherosclerosis -- AA
preliminarypreliminary reportreport”, The”, The JournalJournal ofof Experimental Medicine,Experimental Medicine, 1913)1913)

 StudiesStudies alsoalso suggestsuggest thatthat chemotherapychemotherapy maymay bebe aa riskrisk factorfactor forfor thethe
developmentdevelopment ofof atherosclerosisatherosclerosis..
 ((SajimaSajima T,T, TanabeTanabe AA etet al.al. ImpactImpact ofof platinumplatinum--basedbased chemotherapychemotherapy onon thethe
progressionprogression ofof atherosclerosisatherosclerosis.. ClimatericClimateric 20112011 FebFeb;14 (1): 31;14 (1): 31--40;40; KalabovaKalabova H,H,
MelicharMelichar BB etet al. Intimaal. Intima--mediamedia thicknessthickness,, myocardialmyocardial perfusionperfusion andand laboratorylaboratory riskrisk
factorsfactors ofof atherosclerosisatherosclerosis inin patientspatients withwith breastbreast cancercancer treatedtreated withwith anthracyclineanthracycline--
basedbased chemotherapychemotherapy.. MedMed OncolOncol 20112011 DecDec; 28 (4): 1281; 28 (4): 1281--7)7)

 RadiationRadiation maymay alsoalso induceinduce atherosclerosisatherosclerosis.. RecentRecent epidemiologicalepidemiological
studiesstudies providedprovided evidenceevidence thatthat anan excessexcess riskrisk ofof cardiovascularcardiovascular diseasedisease
cancan bebe associatedassociated withwith moderatemoderate andand lowlow dosedose radiationradiation..
 It isIt is reconizedreconized for morefor more thanthan 5050 yearsyears thethe effectseffects ofof radiationradiation overover thethe
nervousnervous system. Insystem. In thisthis relationshiprelationship W. OW. O CasterCaster fromfrom USUS saidsaid in ain a
SymposiumSymposium onon thethe EffectsEffects ofof IonizingIonizing RadiationRadiation onon thethe NervousNervous SystemSystem
heldheld byby thethe InternationalInternational AtomicAtomic EnergyEnergy AgencyAgency (IAEA), in 1961:(IAEA), in 1961:
 “it“it maymay turnturn outout thatthat a centrala central nervousnervous systemsystem responseresponse isis anan importantimportant
underlyingunderlying factorfactor inin thethe causationcausation ofof manymany ofof thethe commoncommon manifestationsmanifestations ofof
radiationradiation damagedamage””
 (Andrea(Andrea BorghiniBorghini etet al.al. Ionizing radiation and atherosclerosis: Current knowledgeIonizing radiation and atherosclerosis: Current knowledge
and future challenges. Atherosclerosis 2013, V 230; I 1: 40and future challenges. Atherosclerosis 2013, V 230; I 1: 40 –– 47)47)

 Recent studies show that acute myocardial infarction leads to accelerationRecent studies show that acute myocardial infarction leads to acceleration
of atherosclerosis. In our view this happens because the acuteof atherosclerosis. In our view this happens because the acute
sympathetic activity in AMI results in lactic acidosis and lactatesympathetic activity in AMI results in lactic acidosis and lactate
accumulation leading to increased perfusion pressure and effects onaccumulation leading to increased perfusion pressure and effects on
contractility of coronary arteries ,with changes in hemodynamic shearcontractility of coronary arteries ,with changes in hemodynamic shear
stress ending in atherosclerosis as consequence. Mechanism supported bystress ending in atherosclerosis as consequence. Mechanism supported by
the acidity theory of atherosclerosis.the acidity theory of atherosclerosis.
 ((DuttaDutta P,P, CourtiesCourties G,G, WeiWei Y,Y, LeuschnerLeuschner F,F, GorbatovGorbatov R, Robbins CS, Iwamoto Y,R, Robbins CS, Iwamoto Y, etet
al.al. MyocardialMyocardial infarctioninfarction acceleratesaccelerates atherosclerosisatherosclerosis.. NatureNature. 2012 Jul. 2012 Jul
19;487(7407):32519;487(7407):325--9;9; HuiHui Wang, Daniel T.Wang, Daniel T. EitzmanEitzman. Acute myocardial infarction. Acute myocardial infarction
leads to acceleration of atherosclerosis. Atherosclerosis, Volume 229, Issue 1 , Pagesleads to acceleration of atherosclerosis. Atherosclerosis, Volume 229, Issue 1 , Pages
1818--22, July 2013)22, July 2013)

 InIn addition of diabetes and hypertension there are various diseasesaddition of diabetes and hypertension there are various diseases
associated withassociated with atherosclerosis/coronary artery diseaseatherosclerosis/coronary artery disease where thewhere the
common denominator is the elevation of lactic acid or lactate, forcommon denominator is the elevation of lactic acid or lactate, for
example: psoriasis, rheumatoidexample: psoriasis, rheumatoid arthritis, osteoporosisarthritis, osteoporosis and migraine.and migraine.
Certainly the raise in lactic acid/lactate levels might alsoCertainly the raise in lactic acid/lactate levels might also be relatedbe related toto anan
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 ofAtherosclerosis Risk in Communities Carotid MRI Study. International Journal of
Epidemiology 2010;1Epidemiology 2010;1––9; F. E.9; F. E. DemartiniDemartini, P. J. Cannon, W. B., P. J. Cannon, W. B. StasonStason, and J. H., and J. H. LaraghLaragh..
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; GelfandGelfand JM. Patients with severe psoriasis are at increased risk of cardiovascularJM. Patients with severe psoriasis are at increased risk of cardiovascular
mortality: cohort study using the General Practicemortality: cohort study using the General Practice Research DatabaseResearch Database.. EurEur Heart J. 2009Heart J. 2009
Dec 27.;Dec 27.; MalinaMalina L,L, VolekVolek V,V, BielickyBielicky T. The activity of lactate dehydrogenase in theT. The activity of lactate dehydrogenase in the
erythrocytes in psoriasis. Z Hauterythrocytes in psoriasis. Z Haut GeschlechtskrGeschlechtskr. 1969 Oct 1;44(19):877. 1969 Oct 1;44(19):877--9; Roman M. J, et9; Roman M. J, et
al. Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Internal. Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern
Med. 2006; 144: 249Med. 2006; 144: 249--256;256; GobeletGobelet C andC and GersterGerster J. C. Synovial fluid lactate levels in septicJ. C. Synovial fluid lactate levels in septic
and nonand non--septicseptic arthritidesarthritides. Annals of the Rheumatic diseases, 1984, 43, 742. Annals of the Rheumatic diseases, 1984, 43, 742--745;745; DekkersDekkers
JC et al. Elevated sympathetic nervous system activity in patients with recentlyJC et al. Elevated sympathetic nervous system activity in patients with recently
diagnosed rheumatoid arthritis with active disease.diagnosed rheumatoid arthritis with active disease. ClinClin ExpExp RheumatolRheumatol. 2004 Jan. 2004 Jan--
Feb;22(1):63Feb;22(1):63--70.70. LarusLarus SS GudmundssonGudmundsson, Ann I, Ann I ScherScher, Thor, Thor AspelundAspelund, 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, AragaAraga S,S, TakeshimaTakeshima T,T,
Nakashima K. Plasma lactic acid and pyruvic acid levels in migraine and tensionNakashima K. Plasma lactic acid and pyruvic acid levels in migraine and tension--typetype
headache. Headache. 1998 Jan;38(1):39headache. Headache. 1998 Jan;38(1):39--42)42)

 DifferentDifferent necropsy studies have shown that the occurrence ofnecropsy studies have shown that the occurrence of
atherosclerosisatherosclerosis is milder or nonis milder or non--existent in subjects with Downexistent in subjects with Down syndrome.syndrome.
AA reasonable explanation for the reduced incidence ofreasonable explanation for the reduced incidence of atherosclerosisatherosclerosis isis
the altered autonomic regulation in individuals with DS, with effects ofthe altered autonomic regulation in individuals with DS, with effects of
smaller changes insmaller changes in baroreflexbaroreflex sensitivity and insensitivity and in sympathosympatho--excitationexcitation
response.response. The reduced sympathetic response to stress in DS is supportedThe reduced sympathetic response to stress in DS is supported
by the low circulatingby the low circulating catecholaminescatecholamines levels in response to incrementallevels in response to incremental
cyclecycle ergometer exercise in individuals withergometer exercise in individuals with DS.DS.
 ((YläYlä--HerttualaHerttuala S,S, LuomaLuoma J,J, NikkariNikkari T,T, KivimäkiKivimäki T. Down's syndrome andT. Down's syndrome and
atherosclerosis.atherosclerosis. Atherosclerosis,Atherosclerosis, 1989 Apr;76(21989 Apr;76(2--3):3):269269--72; Murdoch72; Murdoch JC, Rodger JC,JC, Rodger JC,
RaoRao SS, Fletcher CD,SS, Fletcher CD, DunniganDunnigan MG. Down's syndrome: an atheromaMG. 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):226226--8;8; IellamoIellamo F,F, GalanteGalante A, et al. Altered autonomicA, et al. Altered autonomic
cardiac regulation incardiac regulation in individualsindividuals with Down syndrome. Am Jwith Down syndrome. Am J PhysiolPhysiol HeartHeart CircCirc
Physiol.Physiol. 2005 Dec;289(62005 Dec;289(6):):H2387H2387--91; Bo91; Bo FernhallFernhall and Mariand Mari OtterstetterOtterstetter. Attenuated. Attenuated
responses toresponses to sympathosympatho--excitation in individuals with Down syndrome. Jexcitation in individuals with Down syndrome. J ApplAppl
PhysiolPhysiol 94: 215894: 2158––2165, 2003);2165, 2003); EberhardEberhard Y,Y, EtarradossiEtarradossi J andJ and TerminariasTerminarias A.A.
Biochemical changes and catecholamine response in Down’s syndrome adolescentsBiochemical changes and catecholamine response in Down’s syndrome adolescents
in relation to incremental maximal exercise. Jin relation to incremental maximal exercise. J MentMent DeficDefic Res 35: 140Res 35: 140--146,146, 1991)1991)

 Necropsy studies have shown that individualsNecropsy studies have shown that individuals suffering from alcoholismsuffering from alcoholism
have a significantlyhave a significantly lower degree of atherosclerosis in the coronarylower degree of atherosclerosis in the coronary
arteries.arteries.
 A paper published in 2002 may have the answer to this question. WilliamA paper published in 2002 may have the answer to this question. William
LovalloLovallo, one of the authors of this, one of the authors of this paper,paper, told in interview totold in interview to EurekAlertEurekAlert
that:“:“Before testing alcoholics for their responses to a publicthat:“:“Before testing alcoholics for their responses to a public--speakingspeaking
task, researchers first needed to establish if their sympathetic nervoustask, researchers first needed to establish if their sympathetic nervous
system was able to respond at all. "This would tell us if their blunting wassystem was able to respond at all. "This would tell us if their blunting was
specific to psychological stressors like public speaking," saidspecific to psychological stressors like public speaking," said LovalloLovallo, "or, "or
due to a generalized autonomic deficit."due to a generalized autonomic deficit."
 TheThe patients reacted as if the social challenge of public speaking had nopatients reacted as if the social challenge of public speaking had no
special meaning for them. So, the sympathetic nervous system in thespecial meaning for them. So, the sympathetic nervous system in the
patients looked normal, but their response to a psychological stressor waspatients looked normal, but their response to a psychological stressor was
almost absent. When faced with a socially meaningful stressor, neitheralmost absent. When faced with a socially meaningful stressor, neither
part of their fightpart of their fight--flight mechanism was workingflight mechanism was working."."
 ((LearyLeary T.T. AtherosclerosisAtherosclerosis,, thethe importantimportant formform ofof arteriosclerosisarteriosclerosis, a, a metabolicmetabolic
diseasedisease.. VolVol 104, N7. JAMA,104, N7. JAMA, 1935;1935; ThomsenThomsen JL.JL. AtherosclerosisAtherosclerosis inin alcoholicsalcoholics..
ForensicForensic SciSci Int. 1995Int. 1995 OctOct 30;75(230;75(2--3):1213):121--3131 andand inin UgeskrUgeskr LaegerLaeger. 1997. 1997 FebFeb
3;159(6):7573;159(6):757--60;60; TeraTera L.L. PankninPanknin, Stacey L., Stacey L. DickensheetsDickensheets, Sara J. Nixon, William R., Sara J. Nixon, William R.
LovalloLovallo.. AttenuatedAttenuated Heart Rate ResponsesHeart Rate Responses toto PublicPublic SpeakingSpeaking inin IndividualsIndividuals WithWith
AlcoholAlcohol DependenceDependence.. AlcoholAlcohol ClinClin. Exp. Res. 2002. Exp. Res. 2002 JunJun; 26 (6): 841; 26 (6): 841

 StudiesStudies have shown that rhesus monkeys submitted to sympatholytic agentshave shown that rhesus monkeys submitted to sympatholytic agents
likelike betablockersbetablockers or bilateral surgical thoracicor bilateral surgical thoracic sympathectomysympathectomy have had ahave had a
marked reduction in the progression ofmarked reduction in the progression of atherosclerosis. Theatherosclerosis. The first randomizedfirst randomized
trial showing thattrial showing that betablockersbetablockers can reduce the rate of progression of carotidcan reduce the rate of progression of carotid
IMT in clinically healthy symptomIMT in clinically healthy symptom--free subjects with carotid plaque wasfree subjects with carotid plaque was
published inpublished in 2001. A2001. A recent pooled analysis data from 4 intravascularrecent pooled analysis data from 4 intravascular
ultrasonography trials involving 1,515 patients has confirmed thatultrasonography trials involving 1,515 patients has confirmed that betablockerbetablocker
therapy is associated with reduced atheromatherapy is associated with reduced atheroma progression. Aprogression. A study by Strawnstudy by Strawn
and colleagues in 1991 have indicated that social disruption is associated withand colleagues in 1991 have indicated that social disruption is associated with
both sympathetic nervous system arousal and indexes of endothelialboth sympathetic nervous system arousal and indexes of endothelial
dysfunction, effects that may be prevented bydysfunction, effects that may be prevented by treatmenttreatment with Bwith B--adrenergicadrenergic
blocking agent.blocking agent. Also interesting is the study showing a decrease inAlso interesting is the study showing a decrease in
glycogenolyticglycogenolytic rate, blood lactate concentration and lactate clearance after Brate, blood lactate concentration and lactate clearance after B--
Adrenergic blockade withAdrenergic blockade with propranololpropranolol, probable a indirect effect of its, probable a indirect effect of its
sympatholyticsympatholytic properties.properties.
 ((LichtorLichtor T et al. 1987.TheT et al. 1987.The sympatheticsympathetic nervousnervous systemsystem andand atherosclerosisatherosclerosis. J. J NeurosurgNeurosurg Dec;67(6):Dec;67(6):906906--
14;14; HedbladHedblad B et al.B et al. LowLow--dosedose metoprololmetoprolol CR/XLCR/XL andand fluvastatinfluvastatin slowslow progressionprogression ofof carotidcarotid intimaintima--
mediamedia thicknessthickness:: MainMain resultsresults fromfrom thethe BetaBeta--BlockerBlocker CholesterolCholesterol--LoweringLowering AsymptomaticAsymptomatic PlaquePlaque
StudyStudy (BCAPS).(BCAPS). CirculationCirculation. 2001. 2001 AprApr 3;103(13):3;103(13):17211721--6.;6.; SipahiSipahi I et al. 2007.I et al. 2007. BB--BlockersBlockers andand
progressionprogression ofof coronarycoronary atherosclerosisatherosclerosis;; PooledPooled analysisanalysis ofof 4 intravascular4 intravascular trialstrials.. AnnalsAnnals ofof InternalInternal
Medicine, 3 July, V147;Medicine, 3 July, V147; IssueIssue 1:1: 1010--18;18; StrawnStrawn WBWB andand allall.. EndothelialEndothelial dysfunctiondysfunction in responsein response toto
psychosocialpsychosocial stress instress in monkeysmonkeys.. CirculationCirculation Research 1991; 68:1270Research 1991; 68:1270--1279;1279; IssekutzIssekutz B Jr. Effect of betaB Jr. Effect of beta––
adrenergic blockade on lactate turnover in exercising dogs. Jadrenergic blockade on lactate turnover in exercising dogs. J ApplAppl PhysiolPhysiol 1984; 57: 17541984; 57: 1754––59)59).

 To our knowledge only one angiographic study assessed data on regressionTo 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 lowtreated with cardiac glycosides. Indeed, cardiac glycosides at low
concentration may lead to stress reduction by the improvement ofconcentration may lead to stress reduction by the improvement of
baroreceptorbaroreceptor function,function, sympathoinhibitorysympathoinhibitory effects,effects, vagomimeticvagomimetic effects andeffects and
decrease in heightened secretion ofdecrease in heightened secretion of catecholaminescatecholamines..
 There are studies showing the existence of potential positive effects of cardiacThere are studies showing the existence of potential positive effects of cardiac
glycosides (glycosides (digoxindigoxin,, digitoxindigitoxin, etc) for the treatment of atherosclerosis., etc) for the treatment of atherosclerosis.
 (Mesquita(Mesquita QHdeQHde,, etet al. Preservação funcional do miocárdio isquêmico peloal. Preservação funcional do miocárdio isquêmico pelo cardiotonicocardiotonico
a longo prazo:a longo prazo: recateterizaçãorecateterização de 29 casos. Medicina de Hoje, março 1978).de 29 casos. Medicina de Hoje, março 1978). GheorghiadeGheorghiade
M, Adams KF,M, Adams KF, ColucciColucci WS.WS. DigoxinDigoxin in the Management of Cardiovascular Disordersin the Management of Cardiovascular Disorders
20042004;; 109109:: 29592959--2964;2964; JagielskaJagielska J. et al.J. et al. DigitoxinDigitoxin elicits antielicits anti--inflammatory andinflammatory and
vasoprotectivevasoprotective properties in endothelial cells: Therapeutic implications for the treatmentproperties in endothelial cells: Therapeutic implications for the treatment
of atherosclerosis?, Atherosclerosis 2009 Oct;206(2):390of atherosclerosis?, Atherosclerosis 2009 Oct;206(2):390--6;6; KolkhofKolkhof P et al. CardiacP et al. Cardiac
glycosides potently inhibit Cglycosides potently inhibit C--reactive protein synthesis in humanreactive protein synthesis in human hepatocyteshepatocytes.. BiochemBiochem
BiophysBiophys ResRes CommunCommun. 2010 Mar 26;394(1): 233. 2010 Mar 26;394(1): 233--9)9)

 RRegression ofegression of coronarycoronary atherosclerosisatherosclerosis in women who were free ofin women who were free of stressstress
showed through the use of serial quantitative angiography;showed through the use of serial quantitative angiography;
 DDecrease ofecrease of carotidcarotid intima media thicknessintima media thickness in African Americans within African Americans with
hypertension submitted to stress reduction through Transcendentalhypertension submitted to stress reduction through Transcendental
MeditationMeditation ;;
 DecreaseDecrease in carotidin carotid intima media thickness inintima media thickness in older persons with multipleolder persons with multiple
factors for coronary heart disease submitted to the Maharishifactors for coronary heart disease submitted to the Maharishi VedicVedic
MedicineMedicine treatmenttreatment ---- which also includes stress reduction throughwhich also includes stress reduction through
Transcendental MeditationTranscendental Meditation program;program;
 YogaYoga intervention retards progression and increases regression ofintervention retards progression and increases regression of
coronary atherosclerosis in patients with severe coronary artery diseasecoronary atherosclerosis in patients with severe coronary artery disease ..
 Slow breathing increasesSlow breathing increases baroreflexbaroreflex sensitivity and reduce sympatheticsensitivity and reduce sympathetic
nervous system with beneficial effects to coronary myocardial disease.nervous system with beneficial effects to coronary myocardial disease.
 *Carlos*Carlos ETBETB MonteiroMonteiro, Acidic environment evoked, Acidic environment evoked by chronicby chronic stress: A novelstress: A novel
mechanism to explainmechanism to explain atherogenesisatherogenesis. Available. Available from Infarctfrom Infarct Combat Project,Combat Project,
January 28, 2008January 28, 2008 at httpat http://://www.infarctcombat.org/AcidityTheory.pdf; Bookwww.infarctcombat.org/AcidityTheory.pdf; Book
“Acidity Theory of Atherosclerosis: New Evidences”, 2012“Acidity Theory of Atherosclerosis: New Evidences”, 2012

 ItIt is interesting to noticeis interesting to notice about theabout the impairment or decrease ofimpairment or decrease of baroreflexbaroreflex
sensitivitysensitivity in front of some key factors for atherosclerosis,in front of some key factors for atherosclerosis, coronarycoronary
myocardial diseasemyocardial disease and stroke, like in ageing, ingestion of sugars,and stroke, like in ageing, ingestion of sugars, inin
specialspecial highhigh--fructose diets, and smoking.fructose diets, and smoking. Indeed thereIndeed there are some studiesare some studies
showing that in bilateral carotid atherosclerosis and in greater intimashowing that in bilateral carotid atherosclerosis and in greater intima--
media thickness themedia thickness the baroreflexbaroreflex sensitivity is reduced or impairedsensitivity is reduced or impaired..
 On the other hand the result of the baroreceptor improvementOn the other hand the result of the baroreceptor improvement is theis the
inhibition of the sympathetic nervous system and activationinhibition of the sympathetic nervous system and activation of theof the
parasympathetic nervousparasympathetic nervous system.system. DrugsDrugs likelike BetablockersBetablockers and Digitalisand Digitalis
glycosides mayglycosides may enhanceenhance baroreflexbaroreflex sensitivitysensitivity withwith possible positivepossible positive
 effects oneffects on atherosclerosis.atherosclerosis.
 (Nasr(Nasr N et al.N et al. BaroreflexBaroreflex sensitivity is impaired in bilateral carotidsensitivity is impaired in bilateral carotid atherosclerosis.atherosclerosis.
Stroke;36:1891Stroke;36:1891--1895;1895; GianorosGianoros PJ et al. Greater intimaPJ et al. Greater intima--media thickness in themedia thickness in the
carotid bulbcarotid bulb is associatedis associated with reducedwith reduced baroreflexbaroreflex sensitivity. Am Jsensitivity. Am J HypertensHypertens..
2002;15(62002;15(6):): 486486--491491;; TruijenTruijen J et al.J et al. BaroreflexBaroreflex sensitivity is higher during acutesensitivity is higher during acute
psychological stresspsychological stress in healthy subjects under Bin healthy subjects under B--adrenergic blockade.adrenergic blockade. ClinClin SciSci
 ((LondLond), Feb 2011; 120(4):161), Feb 2011; 120(4):161--167;167; SchobelSchobel HP et al. 1991.Contrasting effects ofHP et al. 1991.Contrasting effects of
digitalis anddigitalis and dobutaminedobutamine onon baroreflexbaroreflex sympathetic control in normal humans,sympathetic control in normal humans,
CirculationCirculation V84,1118V84,1118--11291129..

 A recent study confirm that the use of beta blockers do not appear to be of anyA 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 arterybenefit 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 ofAlso, the effect of betablockersbetablockers as a treatment for primary hypertension has beenas a treatment for primary hypertension has been
questioned. In a metaquestioned. In a meta--analysis study published at Lancet Journal in 2005 theanalysis study published at Lancet Journal in 2005 the
authors say that the effect ofauthors say that the effect of betablockersbetablockers compared to placebo is less thancompared to placebo is less than
optimum, with no difference for myocardial infarction but with a raised risk ofoptimum, 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 theMoreover in a randomized trial study published in Lancet Journal in 2008 the
authors say that there were more deaths in theauthors say that there were more deaths in the metoprololmetoprolol group than in thegroup than in the
placebo group in patients undergoing nonplacebo group in patients undergoing non--cardiac surgery (129 versus 97 patients).cardiac surgery (129 versus 97 patients).
 So, whileSo, while betablockersbetablockers seems useful in atherosclerosis its poor results in theseseems useful in atherosclerosis its poor results in these
clinical situations might be related to their effects of generalizedclinical situations might be related to their effects of generalized hypocontractilityhypocontractility,,
as suggested by Dr.as suggested by Dr. MesquitaMesquita in 1979.in 1979.
 (Bangalore S,(Bangalore S, StegSteg PHG,PHG, DeedwaniaDeedwania P, et al. Beta blocker use and clinical outcomes in stableP, et al. Beta blocker use and clinical outcomes in stable
outpatients with and without coronary artery disease. JAMA 2012; 308:1340outpatients with and without coronary artery disease. JAMA 2012; 308:1340--1349;1349; LindholmLindholm
LH,LH, CarlbergCarlberg B, Samuelsson O. Should B blockers remain first choice in the treatment ofB, Samuelsson O. Should B blockers remain first choice in the treatment of
primary hypertension? A metaprimary hypertension? A meta--analysis. Lancet 2005;366:1545analysis. Lancet 2005;366:1545--53; POISE study group. Effects53; POISE study group. Effects
of extendedof extended--releaserelease metoprololmetoprolol succinatesuccinate in patients undergoing nonin patients undergoing non--cardiac surgery (POISEcardiac surgery (POISE
Trial): a randomized controlled trial. Lancet 2008; 371: 1839Trial): a randomized controlled trial. Lancet 2008; 371: 1839--47;47; MesquitaMesquita, QH, Book, QH, Book
MyogenicMyogenic Theory of Myocardial Infarction, 1979)Theory of Myocardial Infarction, 1979)

 BaldnessBaldness
 SSevereevere vertex pattern ofvertex pattern of androgeneticandrogenetic alopecia is considered to have analopecia is considered to have an
increased risk of subclinical atherosclerosisincreased risk of subclinical atherosclerosis..
 There is a postulation made in 1997 by MarinoThere is a postulation made in 1997 by Marino SalinSalin, from Italy, telling if, from Italy, telling if
there is excess adrenergic tone in the metabolic system, then there is alsothere 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, glycolysisglycolysis
leads to lactic acid that causes caustic damage to the inner sheath and thisleads 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 CreaseEarlobe Crease
 Diagonal earlobe crease is another external marker for coronary arteryDiagonal earlobe crease is another external marker for coronary artery
disease. Interesting is that the earlobe is one local to determine blooddisease. Interesting is that the earlobe is one local to determine blood
lactate concentration that may be in our opinion the culprit for the earlobelactate 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 Società 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)

 You can find recent videos and powerpoint presentations as well
articles and other information about the acidity theory at:
 http://www.infarctcombat.org/AcidityTheory.html

 InIn thisthis bookbook wewe explore inexplore in
depthdepth thethe riskrisk factorsfactors andand
pathophysiologicalpathophysiological
explanationsexplanations ofof
atherosclerosisatherosclerosis,, underunder thethe
acidityacidity theorytheory pointpoint ofof viewview..
 Our book is beingOur book is being offered foroffered for
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