**4. HIV infection may affect the natural history of atherogenesis**

Individuals infected with human immunodeficiency virus (HIV) have a different condition of life of the population free of infection with regard to morbidity and mortality from pre‐ mature atherosclerosis and cardiovascular, and its related complications[44]-[47].

Atherosclerosis is a systemic disorder characterized by the formation of cholesterol plaques, especially at the level of the intima of the arterial wall. All arteries can be affected, but the clinical consequences are more important at the level of coronary and carotid arteries of the lower limbs (LL).

Arterial disease is chronic, along with coronary artery disease and ischemic stroke, one of three clinical manifestations of the same pathophysiological process: atherothrombosis. The classic risk factors of atherosclerosis are: smoking, hypertension (HTN), diabetes mellitus (DM), hypercholesterolemia, and obesidade[48]. Atherosclerosisisamajor cause ofmortality worldwidemobility, andlow life expectancyis mainly due to heart attack and stroke(CVA)[49]-[51].

The morbidity and mortality among HIV-infected individuals with advanced disease was very high until the advent of potent antiretroviral therapy (HAART), which produced an improvement in quality and increased expectation [52]-[55].

This therapy, however has been associated with a variety of adverse effects, which in‐ clude metabolic changes such as changes lypodistrophy, insulin resistance, lactic acidosis and dislipidemia[46],[56]. All these changes are pro-atherogenic and its consequences are often fatal. The development of cardiovascular disease in HIV-infected individuals is re‐ lated to endothelial dysfunction. This dysfunction and accelerated atherosclerosis is a consequence of HIV itself that activates the endothelial directly or indirectly through production of citocinas[57].

comparisons. Questions that might be raised concerning loss of sensitivity with this type of equipment have already been addressed in a comparison with conventional machines[42].

The carotid artery ensures easy access to the examiner; for its anatomy, as it is a superfi‐ cial artery and follows a more or less straight path along the cervical segment, in addi‐ tion to being a vessel with abundant elastic fibers that respond promptly to

A study with populations at difference ages showed that IMT increases at a rate of [IMTmm

The means for IMT values of common and internal carotids are higher among patients with some risk factor (hypertension, age and smoking). This pattern occurs in normal subjects and patients with hepatosplenic schistosomiasis mansoni clinical and surgical treated, but this phenomenon is not observed in these patients without any treatment[43]. These find‐ ings lend support to the hypothesis that hepatosplenic schistosomiasis mansoni may be a

Individuals infected with human immunodeficiency virus (HIV) have a different condition of life of the population free of infection with regard to morbidity and mortality from pre‐

Atherosclerosis is a systemic disorder characterized by the formation of cholesterol plaques, especially at the level of the intima of the arterial wall. All arteries can be affected, but the clinical consequences are more important at the level of coronary and carotid arteries of the

Arterial disease is chronic, along with coronary artery disease and ischemic stroke, one of three clinical manifestations of the same pathophysiological process: atherothrombosis. The classic risk factors of atherosclerosis are: smoking, hypertension (HTN), diabetes mellitus (DM), hypercholesterolemia, and obesidade[48]. Atherosclerosisisamajor cause ofmortality worldwidemobility, andlow life expectancyis mainly due to heart attack and

The morbidity and mortality among HIV-infected individuals with advanced disease was very high until the advent of potent antiretroviral therapy (HAART), which produced an

This therapy, however has been associated with a variety of adverse effects, which in‐ clude metabolic changes such as changes lypodistrophy, insulin resistance, lactic acidosis and dislipidemia[46],[56]. All these changes are pro-atherogenic and its consequences are often fatal. The development of cardiovascular disease in HIV-infected individuals is re‐ lated to endothelial dysfunction. This dysfunction and accelerated atherosclerosis is a

improvement in quality and increased expectation [52]-[55].

= 0.009 x age+0.35], i.e., it is a biological phenomenon that can be quantified[30].

**4. HIV infection may affect the natural history of atherogenesis**

mature atherosclerosis and cardiovascular, and its related complications[44]-[47].

hemodynamic "stress"[23].

86 Current Trends in Atherogenesis

lower limbs (LL).

stroke(CVA)[49]-[51].

protective factor against atherogenesis[30].

There is evidence that both pathophysiological HIV to antiretroviral therapy may affect the profile lipídico[58],[59], insulina resistance[60],[61] and the response of vasodilatação[62]. The increased mortality in individuals with HIV due to cardiovascular events in young pa‐ tients, often without classic risk factors for atherosclerosis, is cause for concern and the sub‐ ject of new studies[44],[46].

Antiretroviral therapy is associated with pro-atherogenic metabolic abnormalities such as metabolic syndrome, type II diabetes, abnormal distribution of body fat, these conditions al‐ so associated with arterial disease coronariana[63],[64]. Some studies suggest that class of drugs known as protease inhibitors (PI) can be associated with premature atherosclerosis and cardiovascular events, vasculares[47]. It is not clear, but what is the real contribution of ART in HIV and increased risk of cardiovascular disease.

The measurement of intima-media complex (IMT) by ultrasonography (USG) is a nonin‐ vasive marker of early atherosclerosis and may reflect the increased overall cardiovascu‐ lar risk and is associated with increased risk of acute myocardial infarction (AMI) and / or AVC[65]-[67].

The IMT can be used as a predictor of atherosclerotic disease in coronary arteries independ‐ ently of classical risk factors: age, sex, smoking, hypertension, dyslipidemia, diabetes and family history of coronary artery disease (CAD). IMTcan be consideredas a markerfor the evaluation ofatherosclerosissubclínica[68]-[70].

The study using IMT has been performed in patients with acquired immunodeficiency syn‐ drome (AIDS) in the investigation of risk factors for atherosclerosis as an early marker, but there are few studies prospectivos[71],[72].

In AIDS patients the automatic measurement of MIC performed in right and left common carotid, with software determining produces the following measures: average, maximum and minimum (Figure 1). In this same place three manual measurements can be performed. Thus, it is possible to calculate the arithmetic mean of the measure in manual right and left common carotid and the maximum and minimum extent (Figure 2). In the right and left in‐ ternal carotid it can be performed as manual. The gold standard can be represented by the mean of automatic measurements from the right common carotid (RCA) and left common carotid (LCA)[73],[74]. We have measured population of 50 years AIDS patients, the MIC was considered thickened if > 0.8 mm[75] was considered the presence of a thickening dem‐ onstrated plate when WCC > 1.5mm[73],[76].

The ankle-brachial index (ABI) is a simple, noninvasive, high predictive value for peripheral artery disease and has significant association with risk of cardiovascular mortality. It is a good method to be safe, reproducible, low cost, outpatient use and validated in the general population. Early diagnosis of atherosclerosis identifies people at high risk for cardiovascu‐ lar events and thus provides effective treatment and control of factors risco[55].

The reduction of the ABI values below 0.9 is associated with a significantly increased cardio‐ vascular risk, particularly by acute myocardial infarction and ischemic stroke, independent of other factors[77],[78]. The increase in ABI (> 1.3) is due more to changes in arterial compli‐ ance than the stenosis, which would be responsible for a decrease in ABI. The high preva‐ lence of high ABI in patients with HIV may be mediated by the involvement of vascular elasticity as well as the formation of atheromatous plaques. A meta-analysis of six retrospec‐ tive studies the ABI has been studied in patients with HIV. The populations were selected with varying criteria and there was no consensus about the risk factors responsible for ab‐ normal ABI. The increased prevalence of ABI was higher than in the general population. In the population with HIV/AIDS remains whether the high prevalence of altered ABI is asso‐

Atherogenesis: Diseases that May Affect the Natural History "Schistosomiasis and HIV Infection"

http://dx.doi.org/10.5772/54018

89

We selected 70 cases with HIV in use antirratrovirais (ARV) for at least five years of service reference in the State of Pernambuco and 70 controls without HIV, matched by sex and age, which were assessed by automatic measurement of carotid IMT in and ABI. It was taken in‐ to account the classical risk factors of atherosclerosis, anthropometric measurements and treatment with protease inhibitors (PI). We performed the analysis of homogeneity of

The ABI was raised in a single patient in the case group (0.7%) and no change in the control group ABI. The WCC was not thickened in any individual. There was no statistically signifi‐ cant difference between case and control groups with respect to the ABI and the WCC, even when considering the type of treatment. There was no significant difference between the

Maggi et al. evaluating patients with HIV and advocate the hypothesis that CMI is thick‐ ened more in the HIV group, which use the IP protocol is the cause of the thickening and that the lesions found in these patients are similar to arteritis and substantially different from atherosclerotic plaques[66],[69],[71],[72]. The present study does not confirm this hy‐ pothesis of thickening CMI in patients with HIV. In 70 patients there was no thickening in the common carotid, while also presenting the same classic risk factors for atherosclerosis, including having more hypercholesterolemia and hypertriglyceridemia than the control group. One possible explanation for the lack of thickening of the WCC in this population is the fact that the patients are young (mean 40.5 years), having long-term treatment (mean 8.16 years), have fewer risk factors than other atherosclerosis studies and found to be clini‐ cally stable (84% had an undetectable current CV with current median CD4 670.57) with less

It can be concluded that HIV-infected individuals do not run a higher risk of atherosclerosis than the control population, taking into consideration the classical risk factors of atheroscle‐

The result of this study is essential because as the population was very young, phase detec‐ tion of atherosclerotic disease earlier period can be after cutting realized. The follow-up of a cohort for a new sectional assessment later is very important for early detection of athero‐

ciated with increased incidence of cardiovascular events.

groups. The groups were homogeneous at the 95% confidence.

rosis and the specific characteristics of HIV-infected patients.

sclerosis in HIV patients on antiretroviral therapy.

aggression endothelium.

groups regarding presence of atheromatous plaques in the common carotid.

**Figure 1.** Medida automática do CMI em CCD

**Figure 2.** Medida manual do CMI em CCD

The reduction of the ABI values below 0.9 is associated with a significantly increased cardio‐ vascular risk, particularly by acute myocardial infarction and ischemic stroke, independent of other factors[77],[78]. The increase in ABI (> 1.3) is due more to changes in arterial compli‐ ance than the stenosis, which would be responsible for a decrease in ABI. The high preva‐ lence of high ABI in patients with HIV may be mediated by the involvement of vascular elasticity as well as the formation of atheromatous plaques. A meta-analysis of six retrospec‐ tive studies the ABI has been studied in patients with HIV. The populations were selected with varying criteria and there was no consensus about the risk factors responsible for ab‐ normal ABI. The increased prevalence of ABI was higher than in the general population. In the population with HIV/AIDS remains whether the high prevalence of altered ABI is asso‐ ciated with increased incidence of cardiovascular events.

We selected 70 cases with HIV in use antirratrovirais (ARV) for at least five years of service reference in the State of Pernambuco and 70 controls without HIV, matched by sex and age, which were assessed by automatic measurement of carotid IMT in and ABI. It was taken in‐ to account the classical risk factors of atherosclerosis, anthropometric measurements and treatment with protease inhibitors (PI). We performed the analysis of homogeneity of groups. The groups were homogeneous at the 95% confidence.

The ABI was raised in a single patient in the case group (0.7%) and no change in the control group ABI. The WCC was not thickened in any individual. There was no statistically signifi‐ cant difference between case and control groups with respect to the ABI and the WCC, even when considering the type of treatment. There was no significant difference between the groups regarding presence of atheromatous plaques in the common carotid.

**Figure 1.** Medida automática do CMI em CCD

88 Current Trends in Atherogenesis

**Figure 2.** Medida manual do CMI em CCD

Maggi et al. evaluating patients with HIV and advocate the hypothesis that CMI is thick‐ ened more in the HIV group, which use the IP protocol is the cause of the thickening and that the lesions found in these patients are similar to arteritis and substantially different from atherosclerotic plaques[66],[69],[71],[72]. The present study does not confirm this hy‐ pothesis of thickening CMI in patients with HIV. In 70 patients there was no thickening in the common carotid, while also presenting the same classic risk factors for atherosclerosis, including having more hypercholesterolemia and hypertriglyceridemia than the control group. One possible explanation for the lack of thickening of the WCC in this population is the fact that the patients are young (mean 40.5 years), having long-term treatment (mean 8.16 years), have fewer risk factors than other atherosclerosis studies and found to be clini‐ cally stable (84% had an undetectable current CV with current median CD4 670.57) with less aggression endothelium.

It can be concluded that HIV-infected individuals do not run a higher risk of atherosclerosis than the control population, taking into consideration the classical risk factors of atheroscle‐ rosis and the specific characteristics of HIV-infected patients.

The result of this study is essential because as the population was very young, phase detec‐ tion of atherosclerotic disease earlier period can be after cutting realized. The follow-up of a cohort for a new sectional assessment later is very important for early detection of athero‐ sclerosis in HIV patients on antiretroviral therapy.

## **Author details**

Carlos Teixeira Brandt, Emanuelle Tenório A. M. Godoi, André Valença, Guilherme Veras Mascena and Jocelene Tenório A. M. Godoi

Federal University of Pernambuco, Pernambuco, Recife, Brazil

### **References**


[14] Gensini GF, Dilaghi B. The unstable plaque. Eur Heart J Supplements. 2002; (4);

Atherogenesis: Diseases that May Affect the Natural History "Schistosomiasis and HIV Infection"

http://dx.doi.org/10.5772/54018

91

[15] Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic op‐

[16] Stanley RG, Jackson CL, Griffiths K, Doenhoff MJ. Effects of Schistosomamansoni worms and eggs on circulating cholesterol and liver lipids in mice. Atherosclerosis.

[17] La Flamme AC, Harvie M, Kenwright D, Cameron K, Rawlence N, Low YS, McKen‐ zie S. Chronic exposure to schistosome eggs reduces serum cholesterol but has no ef‐ fect on atherosclerotic lesion development. Parasite Immunol. 2007;29(5):259-66.

[18] Lane HA, Smith JC, Davies JS. Noninvasive assessment of preclinical atherosclerosis.

[19] Raitakari OT, Juonala M, Kahonen M, Taittonen L, Laitinen T, Makittorko N, et al. Cardiovascular risk factors in childhood and carotid intima-media thickness in adult‐ hood: The cardiovascular risk in young Finns study. JAMA. 2003; 290(17): 2277-83.

[20] Bonithon-Kopp C, Touboul PJ, Berr C, Leroux C, Mainard F, Courbon D, et al. Rela‐ tion of intima-media thickness to atherosclerotic plaques in carotid arteries. The Vas‐

[21] Ishizu T, Ishimitsu T, Yanagi H, Seo Y, Obara K, Moriyama N, et al Effect of age on carotid arterial intima-media thickness in chilhood. Heart and Vessel. 2004;

[22] Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall. A direct measurement with ultrasound imaging. Circulation. 1986;

[23] Ebrahim S, Papacosta O, Whincup P, Wannamethee G, Walker M, Nicolaides AN, et al. Carotid plaque, intima-media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study. Stroke.

[24] Baldassarre D, Amato Mauro, Bondioli A, Sirtori CR, Tremoli E. Carotid artery inti‐ ma-media thickness measured by ultrasonography in normal clinical practice corre‐

[25] Espínola-Klein C, Hans-Jürgen R, Blankenberg S, Bickel C, Kopp H, Rippin G, et al. Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumoniae, Helicobacter pylori, Cytomegalovirus, or Herpes simplex

[26] WHO. World Health Organization. The Control of Schistosomiasis, Technical Report

lates well with aterosclerotic risk factors. Stroke. 2000; 31(10):2426-38.

virus infection? Stroke. 2002; 31(9):2127-38.

cular Aging Study (EVA). ArteriosclerThrombVasc Biol. 1996; 16(10):310-6.

(Suppl B):22-27.

2009;207(1):131-8.

19(4)189-95.

74(6):1399-1406.

1999; 30(4):841-50.

Series; 1993. p.86.

tions.Nat Med. 2011;17;11:1410-22.

Vasc Health Risk Manag. 2006; 2(1): 19-30.


[14] Gensini GF, Dilaghi B. The unstable plaque. Eur Heart J Supplements. 2002; (4); (Suppl B):22-27.

**Author details**

90 Current Trends in Atherogenesis

**References**

2004;109:III-27–III-32.

2001;15:2623–30.

2002;105:1135-1143.

2002;105:1135-1143.

2011; 22(5): 327–334

Carlos Teixeira Brandt, Emanuelle Tenório A. M. Godoi, André Valença,

[1] Ross R. Atherosclerois - an inflammatory disease. N Engl J Med. 1999; 340:115–126. [2] Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation.

[3] Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and high-

[4] Moghadasian MH, McManus BM, Nguyen LB, Shefer S, Nadji M, Godin DV, Green TJ, Hill J, Yang Y, Scudamore CH, Frohlich JJ. Pathophys- iology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans. FASEB J.

[5] Stoll G, Bendszus M. Inflammation and atherosclerosis: Novel insights Intoplaque formation and destabilization. Downloaded from http://stroke.ahajournals.org∕ 2012.

[6] Ross R. Atherosclerois - an inflammatory disease. N Engl J Med. 1999; 340:115–126. [7] Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation.

[8] Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology

[9] Lonn E, Bosch J, Yusuf S, et al.; HOPE and HOPE‑TOO Trial Investigators. Effects of long‑term vitamin E supplementation on cardiovascular events and cancer: a

[10] Lee SW, Antiga L, Spence JD, Steinman DA. Geometry of the carotid bifurcation pre‐

[11] Lee SW, Antiga L, Spence JD, Steinman DA. Geometry of the carotid bifurcation pre‐

[12] Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation.

[13] GrundtmanC, Wick G. The autoimmune concept of atherosclerosis.CurrOpinLipidol.

Guilherme Veras Mascena and Jocelene Tenório A. M. Godoi

Federal University of Pernambuco, Pernambuco, Recife, Brazil

risk plaque. J Am CollCardiol. 2005;46:937–54.

DOI: 10.1161/01.STR.0000226901.34927.10.

of atherosclerosis. Nature. 2011; 473: 317-325.

randomized controlled trial. JAMA. 2005; 293: 1338-1347.

dicts its exposure to disturbed flow. Stroke. 2008;39:2341–2347.

dicts its exposure to disturbed flow. Stroke. 2008;39:2341–2347.


[27] Brandt CT, Maciel DT, Caneca AOF. Esplenose associada ao tratamento cirúrgico da hipertensão porta esquistossomótica na criança: avaliação de 10 anos. AnFac Med Univ Fed Pernamb. 1999; 44(1):15-20.

[40] Liuba P, Persson J, Luoma J, Ylä-Hertuala S, Pesonen E. Acute infections in children are accompanied by oxidative modification of LDL and decrease of HDL cholesterol, and are followed by thickening of carotid intima-media. European Heart Journal.

Atherogenesis: Diseases that May Affect the Natural History "Schistosomiasis and HIV Infection"

http://dx.doi.org/10.5772/54018

93

[41] Helft G, Worthley SG, Fuster V, Fayad ZA, Zaman AG, Corti R, et al. Progression and regression of atherosclerotic lesions: Monitoring with serial noninvasive magnet‐

[42] Magnussen CG, Fryer J, Laakkonen M, Raitakari OT. Evaluating the use of a portable ultrasound machine to quantify intima-media thickness and flow-mediated dilation: Agreement between measurements from two ultrasound machines. Ultrasound Med

[43] Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu C, Liu C, et al. Reduction in carotid arterial wall thickness using lovastatin and dietary therapy: a randomized controlled

[44] Friis-Moler N, Weber R, Reiss P, Thiébaut R, Kirk O, d'ArminioMonforte A, Pradier C, Morfeldt L, Mateu S, Law M, El-Sadr W, De Wit S, Sabin CA, Phillips AN, Lundg‐ ren JD. Cardiovascular risk factors in HIV patients-association with antirretroviral

[45] Bozkurt B. Cardiovascular toxicity with highly active antirretroviral therapy: review

[46] Grover SA, Coupal L, Gilmore N, Mukherjee J. Impact of dyslipidemia associated with Highly Active Antirretroviral Therapy (HAART) on cardiovascular risk and life

[47] Friis-Moller N, Reiss P, Sabin CA, Weber R, Monforte A, El-Sadr W, Thiébaut R, De Wit S, Kirk O, Fontas E, Law MG, Phillips A, Lundgren JD. Class of antirretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356(17):1723-35. [48] Dedola M, Godoi E, Coppé G, Cambou JP, Cantet C, Mas JL, Guérillot M, Vahanian A, Herrman MA, Jullien G, Leizorovicz A, Boccalon H. Risk factors management in 5708 ambulatory patients suffering from peripheral vascular disease followed in ur‐

[49] Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intimamedia thickness and risk of stroke and myocardial infarction: the Rotterdam Study.

[50] Kung HC, Hoyert DL, Xu J, Murphy SL. Deaths: final data for 2005. Natl Vital Stat

[51] Ministério da Saúde. Estatísticas Vitais. 2006. Brasília. [citado 2009 mai 02]. Disponí‐

[52] Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Asch‐ man DJ, Holmberg SD. Declining morbidity and mortality among patients with ad‐

ic resonance imaging. Circulation. 2002; 105(8):993-8.

clinical trial. Ann Intern Med. 1996; 124(6):548-56.

therapy. Results from DAD study. AIDS. 2003;17(8):1179-93.

of clinical studies. CardiovascToxicol. 2004;4(3):243-60.

ban practic. Arch Mal Coeur Vaiss. 2005;98(12):1177-88.

expectancy. Am J Cardiol. 2005;95(5):586-91.

Circulation. 1997;96(5):1432-7.

vel em:http://www.w3.datasus.gov.br/.

Rep. 2008;56(10):1-120.

2002; 24(6):515-21.

Biol. 2006; 33(9): 1323-9.


[40] Liuba P, Persson J, Luoma J, Ylä-Hertuala S, Pesonen E. Acute infections in children are accompanied by oxidative modification of LDL and decrease of HDL cholesterol, and are followed by thickening of carotid intima-media. European Heart Journal. 2002; 24(6):515-21.

[27] Brandt CT, Maciel DT, Caneca AOF. Esplenose associada ao tratamento cirúrgico da hipertensão porta esquistossomótica na criança: avaliação de 10 anos. AnFac Med

[28] Gillet MPT, Coêlho LCBB. The effect of splenectomy on plasma phosphatidylcholinecolesterolacyltranferase activity and blood lipids in human schistosomiasismansoni.

[29] Facundo HTF, Brandt CT, Owen JS, Lima VLM. Elevated levels of erythrocyte-conju‐ gated dienes indicate increased lipid peroxidation in schistosomiasismansoni pa‐ tients. Braz J Med Biol Res. 2004; 37(7): 957-962. Available from: http://www.scielo.br/

[30] Guimarães AV, Brandt CT, Ferraz A. Complexo miointimal das carótidas comum e interna em portadores de esquistossomose mansônica hepatoesplênica.*Rev. Col. Bras. Cir.*[online]. 2009;36 (4) 292-299. Available from: http://www.scielo.br/scielo. ISSN

[31] Silva SN, Oliveira KF, Brandt CT, Lima VLM. A lipid study of schistosomotic young

[32] Verschuren WM, Jacobs DR, Bloemberg BP, Kromhout D, Menotti A, Aravanis C, et al. Serum total cholesterol and long-term coronary heart disease mortality in differ‐ ent cultures. Twenty-five-years follow-up of the seven countries study. JAMA.1995;

[33] Khovindhunkit W, Memon RA, Feingold KR, Grunfekd C. Infection and inflamma‐ tion-induced proatherogenic changes of lipoproteins. J Infect Dis. 2000; 81(Suppl.3):

[34] Feingold KR, Soued M, Serio MK, Adi S, Moser AH, Grunfeld C. The effect of diet on tumor necrosis factor stimulation of hepatic lipogenesis. Metabolism. 1990;39(6):

[35] Mendall MA, Goggin PM, Molineaux N, Levy J, Toosy T, Strachan D et al. Relation of Helicobacter pylori infection and coronary heart disease. Br Heart J. 1994; 71(5):437-9.

[36] DeStefano F, Anda RF, Kahn HS, Williamson DF, Russell CM. Dental disease and

[37] Yudkin JS, Kumari M, Humphries SE. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis. 2000; 148(2): 209-14.

[38] Sunnemark D, Harris RA, Frostegard J, Orn A. Induction of early atherosclerosis in CBA/J mice by combination of Tripanossomacruzi infection and a high cholesterol

[39] Doenhoff M.J, Stanley RG, Griffiths, Jackson CL. An anti-atherogenic effect of Schis‐ tosomiasismansoni infection in mice associated with a parasite-induced lowering of

risk of coronary heart disease and mortality. BMJ. 1993; 306(6879):688-91.

diet. Atherosclerosis. 2000; 153(2):273-82.

blood total cholesterol.Parasitology. 2003;(9)337-50.

Univ Fed Pernamb. 1999; 44(1):15-20.

Bioch Soc Trans. 1979; 7(5):988-990.

27(4): 131-6.

462-72.

92 Current Trends in Atherogenesis

623-632.

scielo.doi.org/10.1590/S0100-879X2004000700003.

0100-6991. http://dx.doi.org/10.1590/S0100-69912009000400004.

people underwent surgical treatment. Acta Cir. Bras. 2002; 17(4):251-7.


vanced human immunodeficiency virus infection. HIV Outpatient Study Investiga. N Engl J Med. 1998, 338(13): 853-60.

[64] Depairon M, Chessex S, Sudre P, Rodondi N, Doser N, Chave JP, Riesen W, Nicod P, Darioli R, Telenti A, Mooser V. Premature atherosclerosis in HIV-infected individu‐

Atherogenesis: Diseases that May Affect the Natural History "Schistosomiasis and HIV Infection"

http://dx.doi.org/10.5772/54018

95

[65] Simon A, Gariepy J, Chironi G, Megnien JL, Levenson J. Intima-media thickness: a new tool for diagnosis and treatment of cardiovascular risk. J Hypertens. 2002;20(2):

[66] Bots ML, Evans GW, Riley WA, Grobbee DE. Carotid intima-media thickness meas‐ urements in intervention studies design options, progression rates, and sample Size

[67] Barros FS, Pontes SM. Doença carotídea aterosclerótica. In: Engeelhorn CA, Morais Filho D, Barros FS, editores. Guia prático de ultra-sonografia vascular. 1ª ed. Rio de

[68] Lekakis JP, Papamichael CM, Cimponeriu AT, Stamatelopoulos KS, Papaioannou TG, Kanakakis J, Alevizaki MK, Papapanagiotou A, Kalofoutis AT, Stamatelopoulos SF. Atherosclerotic changes of extracoronary arteries are associated with the extent of

[69] Maggi P, Lillo A, Perilli F, Maserati R, Chirianni A. Colour-Doppler ultrasonography of carotid vessels in patients treated with antirretroviral therapy: a comparative

[70] Allison MA, Tiefenbrun J, Langer RD, Wright CM. Atherosclerotic calcification and intimal medial thickness of the carotid arteries.Int J Cardiol. 2005;103(1):98-104. [71] Maggi P, Perilli F, Lillo A, Carito V, Epifani G, Bellacosa C, Pastore G, Regina G. An ultrasound-based comparative study on carotid plaques in HIV-positive patients vs. atherosclerotic and arteritis patients: atherosclerotic or inflammatory lesions? Coron

[72] Maggi P, Perilli F, Lillo A, Gargiulo M, Ferraro S, Grisorio B, Ferrara S, Carito V, Bel‐ lacosa C, Pastore G, Chirianni A, Regina G. Rapid progression of carotid lesions in

[73] Touboul PJ, Hennerici MG, Meairs S, *et al*. Mannheim carotid intima-media thickness

[74] Touboul PJ, Vicaut E, Labreuche J, *et al*. Correlation between the Framingham risk score and intima media thickness: the Paroi Artérielle et Risque Cardio-vasculaire

[75] Engelhorn CA, Engelhorn AL, Cassou MF, *et al*. Espessamento médio-intimal na ori‐ gem da artéria subclávia direita como marcador precoce de risco cardiovascular. *Arq*

[76] Labropoulos N, Ashraf Mansour M, Kang SS, *et al*. Viscoelastic properties of normal and atherosclerotic carotid arteries. *Eur J Vasc Endovasc Surg* 2000;19:221-5.

HAART-treated HIV-1 patients. Atherosclerosis. 2007;192(2):407-12.

consensus (2004-2006). *Cerebrovasc Dis* 2007;23:75-80.

(PARC) study. *Atherosclerosis* 2007;192:363-9.

*Bras de Cardiol*. 2006; 87:609-14.

als-focus on protease inhibitor therapy. AIDS, 2001;15(3):329-34.

considerations: a point of view. Stroke. 2003;34:2985-94.

coronary atherosclerosis. Am J Cardiol. 2000; 85(8):949-52.

Janeiro: Dilivros; 2007. p.17-37.

study. AIDS. 2004;18(7):1023-8.

Artery Dis. 2007;18(1):23-9.

159-69.


[64] Depairon M, Chessex S, Sudre P, Rodondi N, Doser N, Chave JP, Riesen W, Nicod P, Darioli R, Telenti A, Mooser V. Premature atherosclerosis in HIV-infected individu‐ als-focus on protease inhibitor therapy. AIDS, 2001;15(3):329-34.

vanced human immunodeficiency virus infection. HIV Outpatient Study Investiga.

[53] Lewden C, Chene G, Morlat P, Raffi F, Dupon M, Dellamonica P, Pellegrin JL, Katla‐ ma C, Dabis F, Leport C. HIV-infected adults with a CD4 cell count greater than 500 cells/mm3 on long-term combination antirretroviral therapy reach same mortality

[54] Lima VD, Hogg RS, Harrigan PR, Moore D, Yip B, Wood E, Montaner JS. Continued improvement in survival among HIV-infected individuals with newer forms of high‐

[55] Olalla J, Salas D, de la Torre J, Del Arco A, Prada JL, Martos F, Perea-Milla E, García-

[56] Hajjar LA, Calderaro D, Yu PC, Giuliano I, Lima EMO; Barbaro G, Caramelli B. Man‐ ifestações cardiovasculares em pacientes com infecção pelo vírus da imunodeficiên‐

[57] Hürlimann D, Weber R, Enseleit F, Lüscher TF. HIV infection, antirretroviral thera‐

[58] Kannel WB, Giordano M. Long-term cardiovascular risk with protease inhibitors and

[59] Bernal E, Masiá M, Padilla S, Gutiérrez F. High-density lipoprotein cholesterol in HIV-infected patients: evidence for an association with HIV-1 viral load, antirretrovi‐ ral therapy status, and regimen composition. AIDS Patient Care STDS. 2008;22(7):

[60] Mulligan K, Grunfeld C, Tai VW, Algren H, Pang M, Chernoff DN, Lo JC, Schambe‐ lan M. Hyperlipidemia and insulin resistance are induced by protease inhibitors in‐ dependent of changes in body composition in patients with HIV infection. J Acquir

[61] Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by

[62] Hsue PY, Hunt PW, Wu Y, Schnell A, Ho JE, Hatano H, Xie Y, Martin JN, Ganz P, Deeks SG. Association of abacavir and HIV disease factors with endothelial function in patients on long-term suppressive ART. In: Program and abstracts of the 16th Con‐ ference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montreal.

[63] Maggi P, Serio G, Epifani G, Fiorentino G, Saracino A, Fico C, Perilli F, Lillo A, Fer‐ raro S, Gargiulo M, Chirianni A, Angarano G, Regina G, Pastore G. Premature le‐ sions of the carotid vessels in HIV-1-infected patients treated with protease

management of the dyslipidemia. Am J Cardiol. 2004;94(7): 901-6.

HIV protease inhibitor therapy. J Biol Chem. 2000;275(27):20251-4.

rates as the general popul. J Acquir Immune DeficSyndr. 2007, 46(1):72-7.

Alegría J. Ankle-brachial index in HIV infection.AIDS Res Ther. 2009;6:6.

ly active antirretroviral therapy. AIDS. 2007;21(6):685-92.

cia humana. Arq Bras Cardiol. 2005;85(5):363-77.

py, and endothelium. Herz. 2005;30(6):472-80.

Immune DeficSyndr. 2000;23(1):35-43.

inhibitors.AIDS. 2000;14(16):F123-8.

569-75.

Abstract 723.

N Engl J Med. 1998, 338(13): 853-60.

94 Current Trends in Atherogenesis


[77] Leger P, Boccalon H. Bilan d'un artériopathie des membres inférieurs (AMI). In: Boc‐ calon H, editor. Guide Pratique des Maladies Vasculaires, 2a ed. France: Masson; 2001. p.13-18.

**Chapter 5**

**The Evaluation of New Biomarkers of Inflammation and**

Peripheral artery disease is a clinical manifestation of atherosclerosis with significant morbid‐ ity and mortality (Sharma Sharma & Aronow, 2012; Resnick et al. 2004; Diehm et al. 2009). Despite well-recognized significance of traditional risk factors in the initiation and progression of the disease, not all causes and mechanisms leading to disease development have been identified so far. Inflammation, angiogenesis, and endothelial activation are important processes contributing to the pathogenesis of peripheral arterial disease which are related in a complex and interdependent manner (Li et al., 2007; Brevetti et al., 2010; Brevetti Get al.,

Pathophysiologic events in peripheral artery disease are represented by ishaemic tissue damage, and the severity of clinical presentation depends on the site and extent of stenosis and availability of collateral circulation (Meru et al., 2006; Cooke 2008). Angiogenesis and arteriogenesis (collateral growth) are different forms of vessel growth, which contribute to the compensation for an occluded artery. Hypoxia is known to trigger angiogenesis in the setting of ischaemia, whereas fluid shear stress might be the most important stimulus for initiation of collateral growth. Besides these specific initial triggers, angiogenesis and collateral growth share growth factors, chemokines, proteases, and inflammatory cells, which play different

During an tissue ischemia, hypoxia-inducible factor 1 (HIF-1) drives transcriptional acti‐ vation of hundreds of genes involved in vascular reactivity, angiogenesis, arteriogenesis, the mobilization of bone marrow-derived angiogenic cells (Rey & Semenza 2010). The current evidence suggests considerable overlap between the molecular mechanisms and

and reproduction in any medium, provided the original work is properly cited.

© 2013 Perkov et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

distribution, and reproduction in any medium, provided the original work is properly cited.

roles in promoting and refining these processes ( Silvestre et al., 2008).

**Angiogenesis in Peripheral Arterial Disease**

Sonja Perkov, Mirjana Mariana Kardum Paro,

Additional information is available at the end of the chapter

Vinko Vidjak and Zlata Flegar-Meštrić

2003; Brevetti et al., 2008; Findley et al., 2008).

http://dx.doi.org/10.5772/53341

**1. Introduction**

[78] Spácil J, Spácabilová J. The ankle-brachial blood pressure index as a risk indicator of generalized atherosclerosis.SeminVasc Med. 2002;2(4):441-5.

**Chapter 5**
