Open access

Arterial Stiffness: A Review in Type 2 Diabetes

Written By

Mariella Catalano, Giovanni Scandale and Gabriel Dimitrov

Submitted: May 7th, 2012 Published: June 26th, 2013

DOI: 10.5772/56582

Chapter metrics overview

2,643 Chapter Downloads

View Full Metrics

1. Introduction

Diabetes is a growing health problem worldwide in [1]. In a prospective study the risk of cardiovascular death in patients with diabetes, without previous coronary heart disease (CHD) is equal to that of patients with CHD without diabetes, with a higher risk factor in women in [2]. This excessive risk is not explained by classic risk factors for cardiovascular disease such as smoking, LDL-cholesterol, hypertension in [3]. This has led to a search for early markers of vascular dysfunction (arterial stiffness) in diabetic patients that may pre-date the development of overt clinical disease, offer a target for early intervention and delay the progress of cardiovascular disease complications. Arterial walls stiffen with age. Once, the aging-associated changes in arterial structural and functional changes were thought to be part of natural aging, but this concept changed when data emerged showing that these changes are accelerated with coexistent cardiovascular disease. For example, patients with diabetes exhibit increased stiffness even after adjusting for age in [4] and this ‘accelerated’ arterial aging is well confirmed to be a risk. Several non-invasive methods are currently used to assess vascular stiffness. An extensive theoretical review of models underlying the definitions and assessment methods of arterial stiffness estimates have been recently published in [5].

Pulse wave velocity is a recognized marker of large artery stiffness. Increased arterial stiffness may be an important pathway linking diabetes to increased cardiovascular risk in [6]. Indeed, increased arterial stiffness predicts the development of cardiovascular disease and mortality in several groups of patients in [7] and has been shown to be elevated and predict premature mortality in patients with type 2 diabetes (T2DM) in [8]. Abnormalities in rigidity markers have been reported in patients with T2DM in [9,10] although not in all the arteries in [11], and also without T2DM though predisposed to diabetes suggesting that genetic influences operate through a mechanism different from structural alterations where body mass index (BMI), and glucose metabolism may be involved in [12,13,14]. Diabetic patients are subject to a myriad of abnormalities (poor glycaemic control, dyslipidaemia etc) and it is difficult to determine which abnormality accounts for arterial stiffening in [15]. We present the results of an analysis that examined the independent association of PWV c-f with cardiovascular risk factors. This may be useful to interpret its variations and is of clinical relevance, as arterial stiffening is an independent predictor of an increase in cardiovascular risk in [16]. For this reason we used PubMed for bibliographic research from 1990 to 2012 using the key words : diabetes non-insulin dependent, T2DM, “PWVc-f,” “aortic pulse wave velocity,” and “aortic stiffness,” which were combined with the terms determining and predictive. Articles with multiple regression analysis were included to evaluate factors independently associated with PWV c-f without any restriction on sample size or type. Variables not included in the regression analysis model were considered not independently associated with PWV c-f. Pathogenetic mechanisms, pathophysiological implications and strategies to reduce arterial stiffening will be discussed.

Advertisement

2. Pulse wave velocity carotid-femoral measurement

Pulse wave velocity carotid-femoral (PWVc-f) is currently considered the “gold standard” in [5] of aortic distensibility, a biophysical property of the arterial wall that allows the pressure waves generated by the left ventricle (buffering function) to be absorbed. PWVc-f, the velocity of arterial wave propagation between two arterial sites, can be measured non-invasively, is simple to determine, precise and reproducible in [17,18]. PWVc-f is calculated by dividing the distance between the carotid and the femoral artery by the time delay of the arterial pulse between these two arterial sites. The speed at which the pulse wave travels through an arterial segment increases with increasing stiffness in [19].

Advertisement

3. Factors associated with Pulse wave velocity carotid-femoral

Age is a powerful determinant of PWVc.f in [20,21]. The results of this review confirm that this is also the case for patients with T2DM. In particular, age is the main determinant of PWV c-f in the multiple regression analysis in 89% of nineteen studies (Table 1). Age exposes the aortic wall to degenerative phenomena such as collagen accumulation, fragmentation of elastic fibers and calcification of the media responsible for the increase in aortic rigidity in [22,23,24]. This interpretation gives a possible explanation of the relationship with arterial blood pressure that is another major determinant of PWVc-f in 95% of the included studies. Longstanding arterial pulsation in the central artery has a direct effect on the structural matrix proteins, collagen and elastin in the arterial wall, disrupting muscular attachments and causing elastin fibers to fatigue and fracture in [25]. This would explain why age and blood pressure are major determinants of PWV c-f in [26]. It should be stressed that aortic stiffening is not only a consequence of hypertension but is also in itself a pathogenetic mechanism of the disease. Several studies report an independent association between heart rate (HR) and PWVc-f. The underlying mechanism is unknown, however several observations indicate that the rate of elastin fatigue fracture depends on the number of stress cycles that is, the number of heartbeats experienced which may explain the relationship between HR and PWVc-f in [27,28]. The relationship between HR and PWV c-f suggests that HR may be a confounding factor that should be incorporated into any analysis relating to PWVc-f. T2DM was associated with an increase in PWVc-f in some studies in [29,30,31,32,33] but not in others in [34,35,36,37]. One explanation for the variable association of PWVcf with diabetes mellitus is that it is gender dependent, with a stronger association in women than in men in [38]. A relation between duration of diabetes and PWV c-f has also been described in [39,40] although other authors have failed to show this in [41]. Glycaemia and glycate hemoglobin (HbA1c) were associated with an increase in PWV c-f in [42] that persisted in the multivariate analysis. In the study by Smith et al [43] there was a weak association between PWV c-f and fasting plasma glucose that persisted in the multivariate analysis. PWV c-f was unrelated to elements of the metabolic syndrome (waist circumference, BMI, and triglycerides) and smoking. Only in [44] BMI was associated to PWVc-f and waist-hip ratio in Strain et al [45]. More importantly, fasting glucose concentration, 2 h post-challenge glucose and homeostasis model assessment for insulin resistance (HOMA-IR) were independently related to PWV c-f after adjustment for age, gender, mean arterial pressure, HR, BMI, renal function and antihypertensive medication in [46]. Implying hyperglycaemic excursion and insulin resistance play important roles in the pathogenesis of atherosclerosis. Possible contributors to increased arterial stiffening in T2DM include impaired glycaemic control and the formation of advanced glycation. The aforementioned are end products which lead to structural changes in the vessel walls. Kimoto et al 2006 showed that gender is a determinant of PWV c-f. In the study by Smith et al women have greater age-related aorta stiffening than men, a finding consistent with the enhanced vascular risk in women with diabetes. In the study by Taniwaki et al aortic stiffness while increased in females, was not a risk factor of PWV c-f in the multiple regression analysis. None of the selected studies report smoking as a determining factor in patients with T2DM. Dyslipidaemia did not play an important role in atherosclerosis therefore it is plausible that hyperlipidaemia and foam-cell-driven plaque formation may affect vascular wall integrity at a later stage in the pathogenic process in [47]. Increased aortic stiffness was associated with retinopathy and peripheral neuropathy after adjusting for possible confounding variables. Other variables associated with increased aortic stiffness were old age, HR, diabetes duration, 24 h pulse pressure, dyslipidaemia and physical inactivity in [48].

Advertisement

4. Coefficient of determination (R²) values

Thirteen studies (68%) reported R² values, representing the amount of variability in PWVc-f. Furthermore, regression models could predict a part of the variability of PWVc-f (22–73% ) indicating that other factors (e.g. insulin resistance, advanced glycation end-products, genetic factors) may play a more important role in arterial stiffness in T2DM.

Advertisement

5. Pathogenetic mechanism of arterial stiffening

Arterial stiffness depends on the structure and function of the vessel wall. Alterations in the extracellular matrix of the media and adventitia have long been implicated in the pathogenesis of age and blood pressure-related increase in arterial stiffness in [49,50]. Data suggest that such alterations may be caused not only by short-term hyperglycemia, but also by carbonyl and oxidative stress and endothelial dysfunction in [51,52]. Impaired glucose tolerance also enhances nonenzymatic glycation of proteins with covalent cross-linking of collagen (AGEs) and alters the mechanical properties of interstitial tissue of the arterial wall in [53,54]. Chronic hyperglycemia and hyperinsulinemia increases the local activity of renin-angiotensin-aldosterone system (RAAS) and expression of angiotensin type I receptor in vascular tissue in [55] promoting development of wall hypertrophy and fibrosis in [56,57]. In recent years there has been growing evidence of the important role played by inflammation which can influence, by different mechanisms, the increase in arterial stiffness (endothelial dysfunction, smooth muscle proliferation and activation, changes in composition of extracellular matrix) in [58].

Advertisement

6. Pathophysiological implications

The principal function of the arterial system is to deliver an adequate supply of blood to tissues and organs. In performing this primary conduit function, the arteries transform the pulsatile flow generated by ventricular contraction into a continuous flow of blood in the periphery. This latter cushioning function is dependent on the mechanical properties of the arterial walls. Increased aortic stiffness has several detrimental effects on cardiovascular performance. A less distensible aorta cannot efficiently accommodate the blood volume ejected by the left ventricle, which results in high systolic pressure. In addition, diastolic pressure is decreased and pulse pressure (PP) is thus increased. These haemodynamic modification influence ventricular afterload and impair coronary perfusion in [59]. Indeed, PP is more closely predictive of mortality in individuals with T2DM than systolic (SBP) and diastolic blood pressure (DBP) in [60]. PWVc-f seems closely related to PP. Excessive pressure pulsatility enhances regional stress and flow abnormalities in the central aorta and proximal large arteries and may contribute to the propensity for focally severe atherosclerosis in these regions. Thus, excessive aortic stiffness and increased pressure pulsatility contribute to damage the arterial wall and may represent both a cause and a consequence of atherogenesis in [61]. Increased local pulsatile pressure and strain increase the likelihood of plaque rupture and thereby contribute to the increased risk of overt clinical events in individuals with atherosclerotic disease. In addition, high pulsatility may be transferred down to arterioles, resulting in disruption of microcirculation leading to stroke, dementia, and to renal failure in [62,63]. A positive relationship between PP and proteinuria has been observed in [64,65]. Such microvascular disease is accentuated in patients with T2DM.

Advertisement

7. Strategies to reduce arterial stiffening in type 2 diabetes

In patients at high risk of developing CVD, such as diabetic patients, it is important to improve arterial stiffness. There are many studies reporting changes in arterial stiffness after various interventions, either non-pharmacological or pharmacological. Non-pharmacological treatment able to reduce arterial stiffness include exercise training, weight loss, and various dietary modifications, including low-salt diet, moderate alcohol consumption, α-linoleic acid, dark chocolate, and fish oil in [66]. It is still debated whether the reduction in arterial stiffness after antihypertensive treatment is only attributable to blood pressure (BP) lowering, or if additional BP-independent effects are involved. However, renin–angiotensin–aldosterone system (RAAS) inhibitors, such as ACE inhibitors and angiotensin II receptor blockers (ARBs), have been widely suggested to have a BP-independent effect on arterial stiffness in [66,68]. Currently, ARBs are recommended as first-line drugs for hypertension treatment in T2DM patients. Several studies have reported that angiotensin receptor blockers (ARBs) also reduce arterial stiffness in patients with hypertension and T2DM in [69,70]. Fish oil ingestion improved vascular compliance in patients with T2DM by increasing nitric oxide (NO) production or release in [71]. Aerobic exercise has been reported to restore the loss of central arterial compliance and would likely improve arterial stiffening in patients with T2DM in [72]. A combined nutrition and walking program in [73] as well as a pure walking intervention in [74] have also demonstrated prospectively a decrease in arterial stiffness in the middle-aged diabetic population. In T2DM, 3 months of pioglitazone treatment reduced PWVc-f while increasing adiponectin in [75] and lowering C-reactive protein. Interestingly, the decrease of PWVc-f and C-reactive protein levels occurred irrespective of improved diabetic control, suggesting that vascular and antidiabetic effects of glitazones may be partially independent. Studies have shown reduction of arterial stiffness using compounds that affect or break the structure of advanced glycation end-product crosslinks (AGEs) in [76].

Advertisement

8. Conclusions

ReferencesSample (n°)Men%AgeMPWVc-fm/sR2(%)Variables associatedwith PWVc-fOther variables
Tanokuchi et al
1995 34
107 T2DM5459H9,4-Age, SBP,DBP-
Taniwaki et al
1999 39
271 T2DM
285 C
44
51
51
50
U9
7
33Age-Diabetes duration-
Amar et al
20014
247 T2DM,HC5254C8,834Age.SBP,HRApolipoprotein
Aoun et al
200141
122 T2DM
122 Ccontrol
66
66
58
58
C13
12
-Age,MBP-
Kimoto et al
2003 30
161 T2DM,
129 Control
53
43
60
59
N-
-
47Age-SBP-T2DM-
Lacy et al
2004 29
66 T2DM
66 Control
68
68
55
55
S9,3
7,7
73Age. SBP,DBP,HR,T2DMPrevious history of cardiovascular disease
Tedesco et al
2004 42
50 T2DM
85 T2DM -HT
60
39
53
55
C11
13,8
22MBPFPG
Silva et al
2004 37
102 T2DM3755C12,6-Age.24-h SBP-
Smith et al
2005 43
134 T2DM6661S10,255Age,,PP, Diabetes durationHT drugs, ACEI/ARB use
Paini et al
2006 44
126 T2DM5863C18,333Age,SBP,BMI
Kimoto et al
2006 31
434 T2DM with and
without CKD
5662
59
H12,555Age,SBP, T2DM,Sex male, GFR,
non cholesterol HDL
Strain et al
2006 45
51 European T2DM
66 African
Caribbean T2DM
49
36
57
57
C
C
14
15
-Age,SBP,MBP,HR
Age,MBP
Waist:hip ratio
Lee et al
2007 33
18 T2DM
20 Control
66
63
MR8,8
6,2
70Age,SBP,T2DM-
Matsumae et al
2008 40
94 Hemodialysis
with T2DM
148 Hemodialysis
without T2DM
5965H1132SBP, Diabetes duration
Age,SBP,HR,
HbA1c
Duration HD, HbA1c
Saez et al
2008 32
318 Renal transplant
with and
without T2DM
4952S9-Age,SBP,T2DM-
Rahman et al
2008 36
T2DM 30
IGT 30
NG 30
47
47
47
S10,4
9,5
8,7
29Age,SBP2hPPG
Cardoso et al
2009 48
482 T2DM
334
148
38
37
59
67
C<12
>12
-Age,24-hPP,HR,Diabetes durationDyslipidemia,retinopathy,physical inactivity, peripheral neuropathy
Webb et al
2010 46
176 NGM
219 IGR
175 T2DM
58
59
59
55
53
57
U8,9
9,7
10
51Age, MBP,HR Sex Female
FPG,2HPG,HOMA-IR
Naka et al
2012 35
165 T2DM3066S10,225Age, SBP-

Table 1.

Characteristic of studies on PWVc-f included in the review

Arteries stiffen with advancing age, even in the absence of clinically detectable atherosclerotic disease. Diabetes has been shown to accelerate this age associated stiffening in [77] mainly through nonenzymatic glycation, the reaction between glucose and the extracellular matrix proteins in the arterial wall. Nonenzymatic glycation leads to the formation of increased collagen crosslinks that result in increased arterial stiffness in [78]. The results of this review show that in T2DM, the increase in aortic stiffness is independent from other common atherosclerotic risk factors. The principal determinants of PWV c-f are age and arterial blood pressure suggesting that an increase in aortic stiffness could be explained in terms of age and blood pressure. This review has certain limits: First, the studies were cross-sectional, and could not reveal causal relationships. Future studies should include prospective studies to elucidate the contribution of environmental-genetic factors over time to arterial stiffening. Secondly, only studies reporting PWV c-f as a measure of arterial stiffness were included. There is considerable variability in agreement between measures of stiffness and PWVc-f is clinically the most relevant. PWV c-f is easy to measure with specifically designed devices. High aortic stiffness doubles the risk of cardiovascular events or mortality compared to low aortic stiffness, and the predictive value of high PWV c-f is greater in high-risk patients, such as patients with T2DM. PWVc-f expresses the cumulative effect of various factors on the arterial system and their interplay with genetic predisposition. In contrast to cardiovascular risk factors, such as blood pressure or cholesterol, that may fluctuate over time, PWVc-f is relatively stable, since it is mostly influenced by alterations of arterial wall structure. The 2007 European Society of Hypertension & European Society of Cardiology guidelines for the management of hypertension rightfully included increased PWVc-f as subclinical target-organ damage, and recommended aggressive management of patients with high PWVc-f in [79]. The World Health Organization estimates that by the year 2025 more than 300 million people worldwide will have diabetes [80]. Measurement of aortic PWV c-f should be integrated in the examination and risk stratification of patients with T2DM.

M, method, C, compilor; S, SphygmoCor; U, ultrasound; H, Hasegawa method MR, magnetic resonance, N, indicates noninvasivepressure recordings. R2,coefficient of determination, SBP, systolic blood pressure, DBP, diastolic blood pressure, PP, pulse pressure, MBP, mean blood pressure, HR, heart rate, FPG, fasting plasma glucose, T2DM, type 2 diabetes; BMI, body mass index, ACE angiotensin-converting enzyme ARB, angiotensin receptor blocker, GFR glomerular filtration rate, HbA1c, glycate hemoglobin, 2HPG, 2 h post-challenge glucose HOMA-IR, homeostasis model assessment for insulin resistance, IGT impaired glucose tolerance IR insulin resistance, IGR, impaired glucose regulation, HT, hypertensive HC, hypercholesterolemia.

Advertisement

Acknowledgments

We would like to thank Mrs Rotolo MR, (Prof. A. Malliani Library, University of Milan) for her help with the bibliographic research.

References

  1. 1. WildSRoglicGGreenASicreeRKingHGlobal prevalence of diabetes: estimates for the year 2000 and projection for 2030. Diabetes Care20042710471053
  2. 2. WhiteleyLPadmanabhanSHoleDIsles C: Should diabetes be considered a coronary heart disease risk equivalent ? Results from 25 years of follow-up in the Renfrew and paisley Survey. Diabetes Care20052815881593
  3. 3. PyöräläKRelationship of glucose tolerance and plasma insulin in the incidence of coronary heart disease.Results from two population studies in Finland. Diabetes Care19792131141
  4. 4. AmarJRuidavetsJ. BChamontinBDrouetLFerrieres J: Arterial stiffness and cardiovascular risk factors in a population- based study. J Hypertens200119381387
  5. 5. LaurentSCockcroftJVan Bortel L Butourye P, Giannattasio C et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J20062725882605
  6. 6. StehouwerC. DHenryR. MFerreiraIArterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease. Diabetologia20085152739
  7. 7. VlachopoulosCAznaouridisKStefanadisCPrediction of cardiovascular events and all-cause mortality with arterial stiffness. A systematic review and meta-analysis. J Am Coll Cardiol;201055131827
  8. 8. CruickshankKRisteLAndersonS. GWrightJ. SDunnGGosling RG: Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: An integrated index of vascular function? Circulation200210620852090
  9. 9. LehmannE. DGoslingR. GSonksenP. HArterial wall compliance in diabetes. Diabet Med19929114119
  10. 10. SchramM. THenryR. MVan DijkR. AKostenseP. JDekkerJ. Met alIncreased central artery stiffness in impaired glucose metabolism and type 2 diabetes: the Hoorn Study. Hypertension200443176181
  11. 11. CatalanoMScandaleGMinolaMCarzanigaGCarottaMet alElastic properties and structure of the radial artery in patients with type 2 diabetes. Diabetes & Vascular Disease Research20096244248
  12. 12. HenryR. MKostenseP. JSpijkermanA. MDekkerJ. MNijpelsGet alArterial stiffness increases with deteriorating glucose tolerance status: the Hoorn Study. Circulation.200310720892095
  13. 13. MceleavyO. DMccallumR. WPetrieJ. RHigher carotid-radial pulse wave velocity in healthy offspring of patients with type 2 diabetes. Diabetic Med.200421262266
  14. 14. GiannattasioCFaillaMCapraAScanzianiEAmigoniMBoffiLWhistockCGambaPPaleariFManciaGIncreased arterial stiffness in normoglycemic normotensive offspring of type 2 Diabetic parents. Hypertension.200851182187
  15. 15. SalomaaVRileyWKarkJ. DNardoCFolsomA. RNon-insulin-dependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes. The ARIC Study. Atherosclerosis Risk in Communities Study. Circulation19959114321443
  16. 16. BlacherJSafarM. EGuerinA. PPannierBMarchaisS. JLondonG. MAortic pulse wave velocity index and mortality in end-stage renal disease. Kidney Int.20036318521860
  17. 17. AsmarRBenetosATopouchianJLaurentPPannierBBrisacA. MTargetRLevyBAssessment of arterial distensibility by automatic pulse wave velocity measurement. Validation and clinical application studies. Hypertension19952648590
  18. 18. WilkinsonI. BFuchsS. AJansenI. MSprattJ. CMurrayG. DCockcroftJ. RWebb DJ: Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis. J Hypertens19981620792084
  19. 19. OliverJ. JWebb DJ: Noninvasive assessment of arterial stiffness and risk of atherosclerotic events. Arterioscler Thromb Vasc Biol200323554566
  20. 20. AvolioA. PChenS. GWangR. PZhangC. LLiM. FORourkeMF. Effects of aging on changing arterial compliance and left ventricular load in a northern Chinese urban community. Circulation.1983685058
  21. 21. SmulyanHCsermelyT. JMookherjeeSWarner RA: Effect of age on arterial distensibility in asymptomatic humans. Arteriosclerosis19833199205
  22. 22. ZiemanS. JMelenovskyVKassD. AMechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol ;2005
  23. 23. AtkinsonJAge-related medial elastocalcinosis in arteries: Mechanisms, animal models, and physiological consequences. J Appl Physiol200810516431651
  24. 24. JacobM. PExtracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions. Biomed Pharmacother200357195202
  25. 25. GreenwaldS. EAgeing of the conduit arteries. J Pathol.2007211157172
  26. 26. McenieryC. MYasmin, Hall IR, Qasem A, Wilkinson IB, Cockcroft JR.Normal vascular ageing: differential effects on wave reflection and aortic pulse wave velocity-the Anglo-Cardiff Collaborative Trial (ACCT 1). J Am Coll Cardiol.20054617531760
  27. 27. Sa Cunha RPannier B, Benetos A, Siche J-P, London GM, Mallion JM, Safar ME. Association between high heart rate and high arterial rigidity in normotensive and hypertensive subjects. J Hypertens.19971514231430
  28. 28. LantelmePMestreCLievreMGressardAMilonHHeart rate: an important confounder of pulse wave velocity assessment. Hypertension.20023910831087
  29. 29. LacyP. SOBrienD. GStanleyA. GDewarMM, Swales PPR, Williams B. Increased pulse wave velocity is not associated with elevated augmentation index in patients with diabetes. J Hypertens.20042219371944
  30. 30. KimotoEShojiTShinoharaKInabaMOkunoYet alPreferential stiffening of central over peripheral arteries in type 2 diabetes. Diabetes200352448452
  31. 31. KimotoEShojiTShinoharaKHatsudaSMoriKet alRegional arterial stiffness in patients with type 2 diabetes and chronic kidney disease. J Am Soc Nephrol200617224552
  32. 32. SaezA. OKosMWitzkeOKribbenANürnbergerJEffect of new-onset diabetes mellitus on arterial stiffness in renal transplantation. Transpl Int.200821930935
  33. 33. Lee JMSShirodaria C, Jackson CE, Robson MD, Antoniades C et al. Multi-modal magnetic resonance imaging quantifies atherosclerosis and vascular dysfunction in patients with type 2 diabetes mellitus. Diab Vasc Dis Res.200744448
  34. 34. TanokuchiSOkadaSOtaZFactors related to aortic pulse wave velocity in patients with non-insulindependent diabetes mellitus. J Int Med Res199523423430
  35. 35. NakaK. KPapathanassiouKBechlioulisAKazakosNPappasKet alDeterminants of vascular function in patients with type 2 diabetes.Cardiovascular Diabetology201211127134
  36. 36. RahamSIsmailA. AIsmailS. BNaingN. NRahman AR Early manifestation of macrovasculopathy in newly diagnosed never treated type II diabetic patients with no traditional CVD risk factors. Diabetes Res Clin Pract200880253258
  37. 37. SilvaJ. ABarbosaLBertoquiniSMaldonadoJPolóniaJRelationship between aortic stiffness and cardiovascular risk factors in a population of normotensive, white coat normotensive, white-coat hypertensive, sustained hypertensive and diabetic patients. Rev Port Cardiol.20042315331547
  38. 38. De AngelisLMillasseauS. CSmithAVibertiGJonesR. HRitterJ. MChowienczykP. JSex differences in age-related stiffening of the aorta in subjects with type 2 diabetes. Hypertension2004446771
  39. 39. TaniwakiHKawagishiTEmotoMShojiTKandaHMaekawaKNishizawaYMorii H: Correlation between the intima-media thickness ofthe carotid artery and aortic pulse-wave velocity in patients with type 2diabetes. Vessel wall properties in type 2 diabetes. Diabetes Care19992218511857
  40. 40. MatsumaeTAbeYMurakamiGUedaKSaitoTEffects of glucose metabolism on aortic pulse wave velocity in hemodialysis patients with and without diabetes. Hypertens Res.20083113651372
  41. 41. AounSBlacherJSafarM. EMouradJ. JDiabetes mellitus and renal failure: effects on large artery stiffness. J Hum Hypertens200115693700
  42. 42. TedescoM. ANataleFDi Salvo G, Caputo S, Capasso M, Calabro R. Effects of coexisting hypertension and type II diabetes mellitus on arterial stiffness. J Hum Hypertens200418469473
  43. 43. SmithAKarallieddeJDe AngelisLGoldsmithDViberti G: Aortic pulse wave velocity and albuminuria in patients with type 2 diabetes. J Am Soc Nephrol20051610691075
  44. 44. PainiABoutouyriePCalvetDTropeanoA. ILalouxBLaurentSCarotid and aortic stiffness: determinants of discrepancies. Hypertension.200647371376
  45. 45. StrainW. DChaturvediNDockeryFShiffRShoreA. CBulpittC. Jet alIncreased arterial stiffness in Europeans and African Caribbeans with type 2 diabetes cannot be accounted for by conventional cardiovascular risk factors. Am J Hypertens20061988996
  46. 46. WebbD. RKhuntiKSilvermanRGrayL. JSrinivasanBLacyP. SWilliamsBDavies MJ Impact of metabolic indices on central artery stiffness: independent association of insulin resistance and glucose with aortic pulse wave velocity. Diabetologia20105311901198
  47. 47. ZureikMBureauJ. MTemmarMAdamopoulosCCourbonDBeanKTouboulP. JBenetosADucimetie`re P. Echogenic carotid plaques are associated with aortic arterial stiffness in subjects with subclinical carotid atherosclerosis. Hypertension.200341519527
  48. 48. Cardoso CRLFerreira MT, Leite NC, Barros PN, Conte PH, Salles GF. Microvascular degenerative complications are associated with increased aortic stiffness in type 2 diabetic patients. Atherosclerosis2009205472476
  49. 49. GlagovSVitoRGiddensD. PZarinsC. KMicroarchitecture and composition of artery walls: relationships to location, diameter and the distribution of mechanical stress. J Hypertens1992Suppl 6): S101S104.
  50. 50. TayebjeeM. HMacFadyen RJ, Lip GY. Extracellular matrix biology: a new frontier in linking the pathology and therapy of hypertension? J Hypertens2003211222112218
  51. 51. EckelR. HWassefMChaitASobelBBarretEKingGet alPrevention conference VI: diabetes and cardiovascular diseases writing group II: pathogenesis of atherosclerosis in diabetes. Circulation200210513843
  52. 52. BrunoR. MPennoGDanieleGLucchesiDSteaFLandiniLCartoniGTaddeiSGhiadoniLDel Prato S. Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients through endothelial dysfunction. Diabetologia201255184755
  53. 53. BrownleeMCeramiAVlassaraHAdvanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med.198831813151321
  54. 54. AiraksinenK. ESalelaP. ILinnaluotoM. KIkaheimoM. JAnolaKRynanenL. JDiminished arterial elasticity in diabetes: association with fluorescent advanced glycosylation end products in collagen. Cardiovasc Res199327942945
  55. 55. NickenigGRolingJStrehlowKSchnabelPBohmMInsulin induces upregulation of vascular AT1 receptor gene expression by posttranscriptional mechanisms. Circulation19989824532460
  56. 56. JesminSSakumaIHattoriYKitabatakeARole of angiotensin II in altered expression of molecules responsible for coronary matrix remodeling in insulin-resistant diabetic rats. Arterioscler Thromb Vasc Biol.20032320212026
  57. 57. RizzoniDPorteriEGuelfiDMuiesanM. LValentiniUCiminoAGirelliARodellaLBianchiRSleimanIRoseiE. AStructural alterations in subcutaneous small arteries of normotensive and hypertensive patients with non-insulin-dependent diabetes mellitus. Circulation.200110312381244
  58. 58. Maki-petajaK. MWilkinson IB Inflammation and large arteries: Potential mechanisms for inflammation-induced arterial stiffness. Artery Research201265964
  59. 59. NicholsW. WORourkeM. FMcdonalds blood flow in arteries: theoretical, experimental and clinical principles. 5th ed. London: Hodder Arnold;2005
  60. 60. SchramM. TKostenseP. Jvan Dijk RAJM, Dekker JM, Nijpels G, Bouter LM, Heine RJ, Stehouwer CDA. Diabetes, pulse pressure and cardiovascular mortality: the Hoorn study. J Hypertens.20022017431751
  61. 61. SakoHMiuraSKumagaiKSakuKAssociations between augmentation index and severity of atheroma or aortic stiffness of the descending thoracic aorta by transesophageal echocardiography. Circ J20097311511156
  62. 62. MitchellG. FVitaJ. ALarsonM. GPariseHKeyesM. Jet alCross-sectional relations of peripheral microvascular function, cardiovascular disease risk factors, and aortic stiffness: the Framingham Heart Study. Circulation2005112372228
  63. 63. ORourkeM. FSafarME. Relationship between aortic stiffening and microvascular disease in brain and kidney. Cause and Logic of therapy. Hypertension.200546200204
  64. 64. PedrinelliRDell’Omo G, Penno G, Bandinelli S, Bertini A, Di BV, Mariani M: Microalbuminuria and pulse pressure in hypertensive and atherosclerotic men. Hypertension2000354854
  65. 65. IshimuraETaniwakiHTsuchidaTObatakeNEmotoMet alUrinary albumin excretion associated with arterial stiffness rather than thickness in type 2 diabetes. J Nephrol20072020411
  66. 66. LaurentSBoutouyriePRecent advances in arterial stiffness and wave reflection in human hypertension. Hypertension20074912021206
  67. 67. MitchellG. FDunlapM. EWarnicaWDucharmeAArnoldJ. MTardifJ. Cet alLong-term trandolapril treatment is associated with reduced aortic stiffness: The prevention of events with angiotensin converting enzyme inhibition hemodynamic substudy. Hypertension20074912711277
  68. 68. TropeanoA. IBoutouyriePPannierBJoannidesRBalkesteinEet alBrachial pressure-independent reduction in carotid stiffness after long-term angiotensin-converting enzyme inhibition in diabetic hypertensives. Hypertension.2006488086
  69. 69. AsmarRGossePTopouchianJNTelaGDudleyAShepherdGL. Effects of telmisartan on arterial stiffness in type 2 diabetes patients with essential hypertension. J Renin Angiotensin Aldosterone Syst2002317680
  70. 70. KarallieddeJSmithADe AngelisLMirendaVKandraABothaJFerberPVibertiGValsartan improves arterial stiffness in type 2 diabetes independently of blood pressure lowering. Hypertension200851161723
  71. 71. McveighG. EBrennanG. MJohnstonG. DMc DermottB. JMc GrathL. Tet alDietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia199336338
  72. 72. MaddenK. MLockartCCuffDPotterT. FMeneilly G Short-term aerobic exercise reduces arterial stiffness in older adults with Type 2 diabetes, hypertension and hypercholesterolemia. Diabetes Care20093215311535
  73. 73. YamamotoAKatayamaYTomiyamaKHosoaiHHirataFYasudaHA short-term admission improved brachial-ankle pulse wave velocity in type 2 diabetic patients. Diabetes Res Clin Pract200570248252
  74. 74. YokoyamaHEmotoMFujiwaraSMotoyamaKMoriokaTet alShort-term aerobic exercise improves arterial stiffness in type 2 diabetes. Diabetes Res Clin Pract2004658593
  75. 75. SatohNOgawaYUsuiTTagamiTKonoSUesugiHet alAntiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care.20032624932499
  76. 76. KassD. AShapiroE. PKawaguchiMet alImproved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation200110414641470
  77. 77. CameronJ. DBulpittC. JPintoE. SRajkumarCThe aging of elastic and muscular arteries: a comparison of diabetic and nondiabetic subjects. Diabetes Care20032621332138
  78. 78. LakattaE. GArterial and cardiac aging: major shareholders in cardiovascular disease enterprises. Part III: cellular and molecular clues to heart and arterial aging. Circulation2003107490497
  79. 79. ManciaGDe BackerGDominiczakACifkovarRFagardRet alESH-ESC Task force on the management of arterial hypertension. J Hypertens200725110587
  80. 80. ZimmetPAlbertiK. GShawJGlobal and societal implications of the diabetes epidemic. Nature2001414782787

Written By

Mariella Catalano, Giovanni Scandale and Gabriel Dimitrov

Submitted: May 7th, 2012 Published: June 26th, 2013