To investigate the correlation between ultrasonographically evaluated intima-media thickness (IMT) of common carotid artery (CCA) and cardiovascular risk factors for subjects with newly detected, uncomplicated and untreated primary hypertension.
Methods
The study population consisted of 200 subjects (123 men and 77 women, aged 46±7.5 years). Blood pressure was measured in the clinical setting and by 24 h noninvasive ambulatory monitoring. Fasting levels of blood glucose, plasma lipids and lipoproteins, fibrinogen and plasminogen activator inhibitor (PAI)-1 were measured. Ultrasound examination included measurement of far-wall intima-media complex of CCA and morphologic evaluation of occurrence of plaques in carotid and femoral bifurcations.
Results
The prevalence of greater than normal IMT (mean IMT ≥ 0.80 mm) was 22%. Significant univariate correlations to the dichotomy between normal and greater than normal mean IMT were detected for age, smoking, level of LDL cholesterol, level of PAI-1 and total ultrasonographic score. Multivariate logistic regression analysis confirmed the associations between greater than normal mean IMT and plasma concentrations of LDL cholesterol and PAI-1 as well as total ultrasonographic score.
Conclusion
Greater than normal IMT of CCA was more strictly related to other cardiovascular risk factors than it was to blood pressure and was strongly associated with the occurrence of atherosclerotic plaques in carotid and femoral arteries. The role of PAI-1 in intima-media thickening that is emerging suggests that fibrinolytic balance is an important determinant of vessel-wall homeostasis in hypertensive patients.
PearsonJFormgrenJIsraelssonBBerglundG.Ultrasound determined intima-media thickness and atherosclerosis. Direct and indirect validation. $Arterioscler Thromb1994; 14: 261–264.
2.
HeissGSharettARBarnesRChamblessLESzkloMAlzolaC and the ARIC Investigators. Carotid atherosclerosis measured by B-mode ultrasound in populations: associations with cardiovascular risk factors in the ARIC study. Am J Epidemiol1991; 134: 250–256.
3.
WendelhagIWiklundOWikstrandJ.Arterial wall thickness in familial hypercholesterolemia: ultrasound measurement of intima-media thickness in the common carotid artery. Arterioscler Thromb1992; 12: 70–77.
4.
WoffordJLKahlFRHowardGRMcKinneyWMTooleJFCrouseJRIII.Relation of extent of extracranial carotid artery atherosclerosis as measured by B-mode ultrasound to the extent of coronary atherosclerosis. Arterioscler Thromb1991; 11: 1786–1794.
5.
BotsMLHoffmanADe BruynAMDe JongPTVMGrobbeeDE.Common carotid intima-media thickness and lower extremity arterial atherosclerosis. The Rotterdam Study. Arterioscler Thromb1994; 14: 1885–1891.
6.
SalonenJTSalonenR.Ultrasound B-mode imaging in observational studies of atherosclerotic progression. Circulation1993; 87 (suppl II): II56–II65.
7.
SafarMEGirerdXLaurentS.Structural changes of large conduit arteries in hypertension. J Hypertens1996; 14: 545–555.
8.
RomanMJSabaPSPiniRSpitzerMPickeringTGRosenSParallel cardiac and vascular adaptation in hypertension. Circulation1992;86: 1909–1918.
9.
FerraraLAManciniMCelentanoAGalderisiMlannuzziRMarottaTEarly changes of the arterial carotid wall in uncomplicated primary hypertensive patients. Study by ultrasound high-resolution B-mode imaging. Arterioscler Thromb1994; 14: 1290–1296.
10.
SuurkülaMAgewallSFagerbergBWendelhagIWidgrenBWikstrandJ.Ultrasound evaluation of atherosclerotic manifestations in the carotid artery in high risk hypertensive patients. Arterioscler Thromb1994;14: 1297–1304.
11.
GariepyJMassonneauMLevensonJHeudesDSimonAand Groupe PCVMETRA Evidence for in vivo carotid and femoral wall thickening in human hypertension. Hypertension1993; 22: 111–118.
12.
RomanMJPickeringTGPiniRSchwartzJEDevereuxRB.Prevalence and determinants of cardiac and vascular hypertrophy in hypertension. Hypertension1995; 26: 369–373.
13.
MuiesanMLPasiniGFSalvettiMCalebichSZulliRCastellanoMCardiac and vascular structural changes. Prevalence and relation to ambulatory blood pressure in a middle-aged general population in northern Italy: The Vobarno Study. Hypertension1996; 27: 1046–1052.
14.
GirerdXMouradJJCopieXMoulinCAcarCSafarMNoninvasive detection of an increased vascular mass in untreated hypertensive patients. Am J Hypertens1994; 7: 1076–1084.
15.
ErnstEReschKL.Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature. N Engl J Med1993; 118: 956–963.
FusterVBadimonLBadimonJJChesebriJH.The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med1992;326: 242–250.
18.
HamstenAErikssonP.Fibrinolysis and atherosclerosis: an update. Fibrinolysis1994; 8 (suppl 1): 253–262.
19.
GidezLIMillerGJBurnsteinMSlagleSEderHA.Separation and quantitation of subclassess of human plasma high density lipoproteins by a simple precipitation procedure. J Lipid Res1982; 23: 1206–1215.
20.
FriedewaldWTLevyRIFredricksonDS.Estimation of the concentration of low density lipoprotein cholesterol without use of preparative ultracentrifuge. Clin Chem1972; 18: 499–504.
21.
PignoliATremoliEPoliAOrestePPaolettiP.Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation1986; 74: 1399–1406.
22.
FleissJL.The design and analysis of clinical experiments.New York; John Wiley & Sons; 1986. p. 3.
23.
MartignoniATinelliCCenteleghePCatalanoOFrattoniAFalaschiFRepeatability study of ultrasonographic intima-media thickness (IMT) measurement. Int Angiol1997; 16 (suppl 1): 139.
24.
BelcaroANicolaidesANLauroraGCesaroneMRDesanctisMIncandelaLUltrasound morphology classification of the arterial wall and cardiovascular evenets in a 6-year follow-up study. Arterioscl Thromb Vasc Biol1996; 16: 851–856.
25.
Stata Corp. State standard software: Release 5.0.College Station, TX; Stata Corporation; 1987.
26.
Statsoft Inc.STATISTICA for Windows.Tulsa, OK; Statsoft Inc.; 1997.
27.
ZanchettiABondMGHennigMNeissAManciaGDal PalùCRisk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis. J Hypertens1998; 18: 949–961.
28.
SalonenRSalonenJT.Progression of carotid atherosclerosis and its determinants: an ultrasonographic study. Atherosclerosis1990; 81: 33–40.
29.
Bonithon-KoppCTouboulP-JBerrCLerouxCMainardFCourbonD. Relation of intima-media thickness to atherosclerotic plaques in carotid arteries. The Vascular Aging (EVA) Study. Arterioscler Thromb Vasc Biol1996;16: 310–316.
30.
SalonenRSalonenJT.Determinants of carotid intima-media thickness: a population based ultrasonography study in eastern Finnish men. J Intern Med1991; 229: 225–231.
31.
Bonithon-KoppCScarabinPYTaquetATouboulP-JMalmejacAGuizeL.Risk factors for early carotid atherosclerosis in middle-aged French women. Arterioscler Thromb1991; 11: 966–972.
32.
ArnettDKTyrolerHABurkeGHutchinsonRHowardGHeissG for the ARIC Investigators. Hypertension and subclinical carotid artery atherosclerosis in black and whites. The Atherosclerosis Risk in Communities Study. Arch Intern Med1996, 156: 1983–1989.
33.
LemneCJogestrandTDe FaireU.Carotid intima-media thickness and plaque in borderline hypertension. Stroke1995; 26: 34–39.
34.
SabaPSCuccuruLPetrettoLGanauA.Carotid plaque is not preceded by intima-medial thickening in hypertension. J Hypertens1997; 15 (suppl 4): S58.
35.
AllanPLMowbrayPILeeAJFowkesFG.Relationship between intima-media thickness and symptomatic and asymptomatic peripheral arterial disease. The Edinburgh Artery Study. Stroke1997; 28: 348–353.
36.
AlessiMCJuhan-VagueIDeclerckPJAnfossoFGueunounECollenD.Correlation between t-PA and PAI-1 antigen and activity and tPA/PAI-1 complexes in plasma of control subjects and of patients with increased tPA or PAI-1 levels. Thromb Res1990; 60: 509–516.
37.
HamstenAWalldiusGBlombackMDe FaireUDahlenG.PAI in plasma: risk factor for recurrent myocardial infarction. Lancet1987; ii: 3–9.
38.
ThompsonSGKienastJPykeSDMHaverkateFVan de LooJCWfor the European Concerted Action on Thrombosis and Diabilities Angina Pectoris Study Group. Hemostatic factors and the risk of myocardial infarction and sudden death in patients with angina pectoris. N Engl J Med1995;332: 635–641.
39.
SalomaaVStinsonVKarkJOFolsomARDavisCEWuKK.Association of fibrinolytic parameters with early atherosclerosis. The ARIC Study. Circulation1995; 91: 284–290.
40.
FolsonARPankowJSWilliamsRREvansGWProvinceMAEckfeldtJH.Fibrinogen, PAI-1 and carotid wall intima media thickness in the NHLBI Family Heart Study. Thromb Haemost1998; 79: 400–404.
41.
AgewallSWikstrandJSuurkulaMTengbornLFagerbergB.Carotid artery wall morphology, haemostatic factors and cardiovascular disease. An ultrasound study in men at high and low risk for atherosclerotic disease. Blood Coagul Fibrinol1994; 5: 895–904.
42.
HaffnerSMD'AgostinoRMykkanenLSavagePJBergmanRNO'LearyDProinsulin and insulin concentrations in relation to carotid wall thickness. Insulin Resistance Atherosclerosis Study. Stroke1998;29: 1498–1503.
43.
JunkerRHeinrichJSchilteHErrenMAssmannG.Hemostasis in normotensive and hypertensive men: results of the PROCAM Study. J Hypertens1998;16: 917–923.
44.
EliassonMJanssonJ-HNilssonPAsplundK.Increased levels of tissue plasminogen activator antigen in essential hypertension. A population-based study in Sweden. J Hypertens1997; 15: 349–356.
45.
CigoliniMTargherGSeidellJCTonoliMSchiavonRAgostinoGRelationship of blood pressure to fibrinolysis: influence of anthropometry, metabolic profile and behavioural variables. J Hypertens1995;13: 659–666.
46.
ToftIBønaaKHIngebretsenOCNordøyABirkelandKIJenssenT.Gender differences in the relationship between plasma plasminogen activator inhibitor-1 activity and factors linked to the insulin resistance syndrome in essential hypertension. Arterioscler Thromb Vasc Biol1997; 17: 553–559.
47.
EtzmanDTNabelEGGordonDFayWPRekterMDGinsburgD.Atherosclerosis in transgenic mice that either overexpress or lack the murine plasminogen activator inhibitor-1 gene. Circulation1996; 94 (suppl 1): I460.
48.
XiaoQDantonMJSWitteDP.Plasminogen deficiency accelerates vessel wall disease in mice predisposed to atherosclerosis. Proc Natl Acad Sci USA1997; 94: 10335–10340.
49.
ChristGHufnaglPKaunCMundiglerGLauferGHuberKAntifibrinolytic properties of the vascular wall. Dependence on the history of smooth muscle doublings in vitro andin vivo. Arterioscler Thromb Vasc Biol1997; 17: 723–730.
50.
VaughanDE.Fibrinolytic balance, the renin-angiotensin system and atherosclerotic disease. Eur Heart J1998; 19 (suppl G): G9–G12.
