This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Westendorp, I. C. D. Articles by Witteman, J. C. M. Search for Related Content PubMed PubMed Citation Articles by Westendorp, I. C. D. Articles by Witteman, J. C. M. Related Collections Pathophysiology Risk Factors Doppler ultrasound, Transcranial Doppler etc.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:713-717.)
© 1999 American Heart Association, Inc.

Original Contributions

Menopausal Status and Distensibility of the Common Carotid Artery

Iris C. D. Westendorp; Michiel L. Bots; Diederick E. Grobbee; Robert S. Reneman; Arnold P. G. Hoeks; Nicole M. Van Popele; Albert Hofman; Jacqueline C. M. Witteman

From the Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam (I.C.D.W., M.L.B., N.M.V.P.); the Julius Center for Patient Oriented Research, Utrecht University, Utrecht (M.L.B., D.E.G.); and the Departments of Physiology (R.S.R.) and Biophysics (A.P.G.H.), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.

Correspondence to I.C.D. Westendorp, MD, Department of Epidemiology and Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail westendorp{at}epib.fgg.eur.nl

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Abstract—Although several studies have shown that exogenous estrogens have beneficial effects on arterial characteristics, the effect of endogenous estrogen on the vascular system is still unknown. In this study, distensibility, an indicator of arterial elasticity, of the common carotid artery was compared in pre- and postmenopausal women. The study comprised 93 premenopausal and 93 postmenopausal women of similar age (range, 43 to 55 years). Women were selected from respondents to a mailed questionnaire about the menopause, which was sent to all women aged 40 to 60 years in the Dutch town of Zoetermeer (n=12 675). Postmenopausal women who were at least 3 years past natural menopause or whose menses had stopped naturally before age 48, were age-matched with premenopausal women with regular menses and without menopausal complaints. The selection aimed at maximizing the contrast in estrogen status between pre- and postmenopausal women of the same age. Distensibility of the carotid artery was measured noninvasively with B-mode ultrasound and a vessel wall movement detector system. Arterial distensibility is expressed as the change in arterial diameter (distension, D) with the cardiac cycle, adjusted for lumen diameter, pulse pressure, and mean arterial blood pressure. Compared with premenopausal women, postmenopausal women had significantly lower arterial distension (D 370.5 µm [SE 9.5] versus 397.3 µm [SE 9.6]). These results suggest that the distensibility of the common carotid artery is negatively affected by natural menopause in presumed healthy women.

Key Words: menopause • distensibility • stiffness • carotid artery • cardiovascular disease

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
The incidence of cardiovascular disease in women rises sharply after middle age, and menopause is thought to be a major determinant of this increase.^{1 2 3} The mechanism through which menopause exerts its effect on the cardiovascular system remains largely unexplained. Unfavorable effects on lipid metabolism have been considered a major intermediary. However, recent studies have increasingly emphasized the direct beneficial effects of estrogens on the arterial wall. In experimental studies in animals, estrogen replacement had direct vasodilatory effects^{4 5 6} and was shown to affect the structure and mechanical properties of large arteries. Improved endothelial function has been shown after hormone replacement therapy in women^{7 8 9} and after estrogen use in transsexual men.^{10 11} Use of estrogens in premenopausal women with coronary artery disease had a beneficial effect on exercise induced myocardial ischemia.¹²

Few studies have addressed the effects of endogenous estrogens and natural menopause on the dynamic characteristics of the arterial system. Although changes in distensibility were not found during the menstrual cycle,¹³ going through menopause has shown to negatively affect the elastic properties of the aortic root in hypertensive women,¹⁴ and time since menopause was inversely related to the pulsatility index in the carotid arteries¹⁵ and several parameters of aortic flow.¹⁶ In the current study, we examined the relation between natural menopause and arterial distension in the common carotid artery.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Study Population
Selection of participants in this study was aimed at maximizing the contrast in estrogen status in pre- and postmenopausal women of the same age (Figure 1). A questionnaire was sent by mail to all women aged 40 to 60 years living in the Dutch town of Zoetermeer, The Netherlands (n=12 675). The questionnaire included questions about menopausal status, medical history, medication use, and smoking behavior. The response rate was 54%. The selection of pre- and postmenopausal women was based on the questionnaire. Women with a hysterectomy and/or unilateral or bilateral oophorectomy (n=1551) and women with missing information on type or date of menopause (n=233) were excluded. Women who had 1 or more bleedings in the past 12 months were considered premenopausal (n=3829). Premenopausal women who reported irregular monthly bleeding (n=938) and women who reported the presence of climacteric symptoms, defined as perspiration and/or hot flushes (n=1645), were excluded from the current study. Furthermore, premenopausal women who reported use of hormone replacement therapy or use of oral contraceptives within 6 months before the onset of the clinical examination were excluded (n=423). The total number of premenopausal women excluded for the above mentioned reasons was 2191, leaving 1638 eligible premenopausal women.

View larger version (10K): [in this window] [in a new window]   Figure 1. Schematic presentation of the selection procedure of the study population. 1, Eligible were women with regular menses and no climacteric symptoms who did not use hormone replacement therapy or oral contraceptives in the past 6 months. Subsequently women who smoked, who had diabetes mellitus, or who used antihypertensive or cholesterol lowering drugs were excluded. 2, Eligible were women whose menses had ceased naturally more than 12 months ago and who had not used hormone replacement therapy. Subsequently women who smoked, who had diabetes mellitus, or who used antihypertensive or cholesterol lowering drugs were excluded. 3, Women who no longer fulfilled the criteria at the moment of examination were excluded.

Women were considered to have had natural menopause if their menses had ceased naturally for at least 12 months (n=1242). Women who reported a history of hormone replacement therapy for over 6 months or use of female hormones within 6 months before the onset of the clinical examination and women who reported cessation of bleeding immediately on stopping hormones were excluded (n=241). The total number of postmenopausal women excluded, including those with missing values on hormone use, was 284, leaving 958 eligible postmenopausal women.

Of the remaining women, we additionally excluded women reporting diabetes mellitus (13 [0.8%] premenopausal and 16 [1.7%] postmenopausal women), use of antihypertensive medication (31 [1.9%] premenopausal and 35 [3.7%] postmenopausal women), use of cholesterol lowering drugs (3 [0.2%] premenopausal and 20 [2.1%] postmenopausal women), and current smoking of 5 cigarettes per day (302 [18.4%] premenopausal and 218 [22.8%] postmenopausal women).

To create a sharp contrast in estrogen status we selected women with either an early or a late natural menopause. Postmenopausal women who were 3 years after menopause or whose menses had stopped 3 years before the average age of menopause (51 years) were age-matched with premenopausal women with regular menses and without menopausal complaints. If it was not possible to find a match within the same year of age, a match was taken from an adjacent year. If 1 of a matched pair was unwilling to participate, a new match was sought. Women were invited for study participation on average 15 months after return of the questionnaire. Out of 424 invited women, 138 were excluded because they no longer fulfilled the inclusion criteria, or no proper replacement match could be found. The primary reasons for no longer fulfilling the inclusion criteria were irregular menses or climacteric symptoms (n=62) and use of female hormones (n=26). Additionally, we excluded women with a history of cardiovascular disease (1 woman with myocardial infarction and 1 with stroke). Sixty-two women (15%) were unwilling to participate and 36 could not be reached. This left 93 pre- and 93 postmenopausal women aged 43 to 55 years who participated in the study. All women gave written informed consent, and the study was approved by the appropriate local institutional committees on ethical practice.

Measurements
During a visit at the research center, a medical history was taken by a physician. Height, weight, and waist and hip circumference were measured with indoor clothes without shoes. Body mass index (weight/height²) and waist to hip ratio were computed. Data on alcohol drinking habits and cigarette smoking history were obtained by a questionnaire. Serum total cholesterol was measured with an automated enzymatic method using the CHOD-PAP High Performance reagent kit from Boehringer Mannheim.

The vessel wall motion of the right common carotid artery was by means of a Duplex scanner (ATL Ultramark IV, operating frequency 7.5 MHz) connected to a vessel wall movement detector system (Wall Track System). The details of this technique have been described elsewhere.^{17 18} Briefly, this system enables the transcutaneous assessment of the displacement of the arterial walls during the cardiac cycle and, hence, the time-dependent changes in arterial diameter relative to its diastolic diameter at the start of the cardiac cycle. Subjects were instructed to refrain from smoking and consuming coffee, tea, alcohol, or pain medication on the day of measurement and from taking alcohol on the day before. Subjects were placed in supine position with the head tilted slightly to the contralateral side for the measurements in the carotid artery. A region at 1.5 cm proximal to the origin of the bulb of the carotid artery was identified using B-mode ultrasonography. Based on the B-mode recording an M-line perpendicular to the artery was selected, and the received radio frequency signals were recorded over 5 cardiac cycles and digitally stored. The displacement of the arterial walls was obtained by processing the radio frequency signals originating from 2 selected sample volumes positioned over the anterior and posterior walls. The successive values of the end-diastolic diameter, the absolute stroke change in diameter during systole (D), and the relative stroke change in diameter ([D]/end-diastolic diameter) were computed from the recording during 5 cardiac cycles. With this system a wall displacement of a few micrometers can be resolved.¹⁷ All measurements were performed by a single observer. A reproducibility study was performed in which 14 participants underwent a second examination within 1 month from the initial examination of the right carotid artery. The coefficient of variation for the absolute diameter change and the lumen diameter was 8.5% and 1.2%, respectively. Measurements were restricted to the right side to save time, as no significant differences in artery wall properties between the right and the left common carotid artery were found.

At the time of the ultrasound examination, blood pressure was measured with a Dinamap automatic blood pressure recorder. Blood pressure was read 4 times at the right upper arm during the measurement session, and the mean was taken as the subjects reading. Pulse pressure was defined as systolic blood pressure minus diastolic blood pressure. Mean arterial pressure was calculated as diastolic blood pressure+(pulse pressure/3).

Statistical Analysis
Linear regression analysis was used to estimate the differences in characteristics between pre- and postmenopausal women. The difference in distension of the carotid arteries between pre- and postmenopausal women was also estimated using linear regression analysis with distension as the dependent variable. Adjustments were made for diastolic lumen diameter and pulse pressure by including these parameters as independent variables in the regression model. This component model allows the inclusion of mean arterial pressure as an additional covariate to account for its effect as well as for pulse pressure.^{19 20 21} Also, additional adjustment could be made for age.

In a separate analysis, the relation between distension and time since menopause was estimated using linear regression analysis adjusting for age, diastolic lumen diameter, pulse pressure, and mean arterial pressure. As the dependent variable, a newly created ordered variable was used, which consisted of the following 3 groups of postmenopausal women: women up to 4 years after menopause, women 5 to 8 years after menopause, and women 9 to 12 years after menopause. A test of significance for the coefficient of this ordered variable was considered to be a test for trend. If a woman could recall the year but not the exact date of onset of menopause, the date was approximated and set on the first of July of that year. Statistical significance was considered to be present when P<0.05.

	Results

Top Abstract Introduction Methods Results Discussion References

 
General characteristics of pre- and postmenopausal women are outlined in Table 1. Among postmenopausal women, the mean number of years after menopause was 5.4 (SD=3.0), and ranged from 1.3 to 12.8. Age, height, weight, body mass index, waist hip ratio, alcohol consumption, smoking, blood pressure, and pulse pressure and frequency were not significantly different between the t2 groups (Table 1 and 2). Total cholesterol was significantly higher in postmenopausal women. The end-diastolic lumen diameter was larger in postmenopausal women (6.73 mm) compared with premenopausal women (6.59 mm), but this difference did not reach statistical significance (Table 2).

View this table: [in this window] [in a new window]   Table 1. General Characteristics of Pre- and Postmenopausal Women

View this table: [in this window] [in a new window]   Table 2. Arterial Characteristics in Pre- and Postmenopausal Women

When comparing the 2 study groups, a significant 7.2% decrease in distension was found in postmenopausal women (D 370.5 µm [SE 9.5]) compared with premenopausal women (D 397.3 µm [SE 9.6]), adjusted for age, diameter during diastole, pulse pressure, and mean arterial pressure (Table 2).

When women were categorized in 3 groups by time since menopause, distension in women up to 4 years after menopause was 379.6 µm (SE 15.9), in women 5 to 8 years after menopause distension was 371.0 µm (SE 15.4), and in women 9 to 12 years after menopause distension was 359.6 µm (SE 22.9), adjusted for age, diastolic lumen diameter, pulse pressure, and mean arterial pressure (Figure 2). This shows that distension tended to decrease with time since menopause, but the changes did not reach statistical significance (test for trend P=0.22).

View larger version (14K): [in this window] [in a new window]   Figure 2. Distension, adjusted for diastolic lumen diameter, pulse pressure, and mean arterial pressure, in premenopausal and 3 groups of postmenopausal women (test for trend, P=0.22).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The results of the current study show that the distensibility of the common carotid artery is significantly lower in postmenopausal women than in premenopausal women of the same age, indicating increased arterial stiffness after menopause.

In studying the effect of menopause, age is an important confounding factor. By a rigorous selection procedure in the current study, we composed a population of age-matched pre- and postmenopausal women from a general population. Because of our stringent inclusion and exclusion criteria, the effect of misclassification of menopausal status is likely to be small. Some misclassification of age of menopause may have occurred, as these assessments were based on self-reports. The slight age difference between the study groups after age-matching was dealt with by further adjustment in the analyses. To exclude potential bias due to other factors, such as smoking, lipid lowering medication, antihypertensive medication, current or recent use of hormone replacement therapy or oral contraceptives, or diabetes, we excluded all women with 1 or more of these confounders and furthermore restricted the study to women who had experienced a natural menopause.

We measured distension in the carotid artery and adjusted for pulse pressure measured in the brachial artery. We thereby assume that pulse pressure measured in the brachial artery is representative of pulse pressure in the carotid artery. In dogs, it has been demonstrated that pulse pressure in the brachial artery is linearly related to blood pressure in the carotid artery over a wide range of blood pressures.²² It is known that the arterial pressure waves undergo transformation in the arterial tree, and therefore, the pulse pressure is higher in the brachial artery than in more central vessels.²³ With increasing age, however, this difference between central and peripheral pulse pressure decreases. It is not known whether the overestimation of pulse pressure measured at the brachial artery differs between pre- and postmenopausal women. If, in line with the decreasing difference seen with age, the overestimation of pulse pressure is less in postmenopausal women, then the true difference in distensibility between the 2 groups would be even larger than estimated in our study.

Various studies suggest sex differences in mechanical properties of the large arteries during the reproductive years, but not thereafter,^{24 25 26} and a steeper decline in distensibility in women than in men in the age range of 45 to 60 years.²⁷ This suggests, but does not yet definitively prove, the influence of menopause on artery wall properties. Studies aimed directly on the relation between natural menopause and artery wall properties are limited. Gangar et al¹⁵ found that the pulsatility index, representing impedance to blood flow distal to the point of measurement in the internal carotid artery, decreased with time since menopause. Taquet et al²⁸ could not show a relationship between menopausal status and aortic pulse wave velocity in 429 women, but the population consisted of perimenopausal women and therefore the contrast in estrogen levels between pre- and postmenopausal women may have been small. In 1 study, a decrease of elastic properties of the aorta was found in a small group of hypertensive women going through menopause during 3 years of follow-up, compared with age-matched women who remained premenopausal during the same period.¹⁴ In our study, decreased distensibility after natural menopause is demonstrated among presumed-healthy women.

The mechanisms through which menopause affects mechanical properties of the arteries are largely unknown. Specific binding of estrogens to receptors in endothelial and vascular smooth muscle cells has been demonstrated in different vascular beds in animals and in humans.^{29 30} Estrogen might change the structure of the arterial wall. In vitro investigations as well as animal studies showed that estrogens decrease collagen production and decrease the elastin/collagen ratio.^{31 32 33} We found a slightly increased lumen diameter in postmenopausal compared with premenopausal women, which may be indicative of remodeling of the vessel wall.³⁴

Whether loss of distensibility is an early marker for asymptomatic atherosclerotic changes or whether it reflects other structural changes of the arterial wall is still a matter of debate.^{35 36 37 38} Decreased distensibility is unfavorably associated with age^{27 39} and with several cardiovascular risk factors, like cholesterol⁴⁰ and hypertension.^{28 41} Loss of distensibility in elastic arteries has been shown to be associated with an increased risk of cardiovascular disease in cross-sectional studies.^{42 43} Longitudinal data on the effect of decreased distensibility on cardiovascular morbidity or mortality are, however, still awaited.

In conclusion, our findings suggest that natural menopause adversely affects the distensibility of the common carotid artery. This may indicate one of the mechanisms through which menopause adversely affects cardiovascular disease risk in women after middle age.

	Acknowledgments

 
The study was supported by a grant from the Netherlands Heart Foundation, The Hague, The Netherlands (Grant No. 94.054) (to J.C.M.W.). We thank Jeannette Vergeer-Drop for carrying out the laboratory measurements and Toos Stehmann and Inge Haumersen for data collection.

Received July 16, 1998; accepted September 14, 1998.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Kannel WB, Hjortland MC, McNamara PM, Gordon T. Menopause and risk of cardiovascular disease: the Framingham study. Ann Intern Med. 1976;85:447–452.
2. Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987;316:1105–1110.[Abstract]
3. Van der Schouw YT, Van der Graaf Y, Steyerberg EW, Eijkemans JC, Banga JD. Age at menopause as a risk factor for cardiovascular mortality. Lancet. 1996;347:714–718.[Medline] [Order article via Infotrieve]
4. Magness RR, Rosenfeld CR. Local and systemic estradiol-17 beta: effects on uterine and systemic vasodilation. Am J Physiol. 1989;256:E536–E542.[Abstract/Free Full Text]
5. Williams JK, Adams MR, Klopfenstein HS. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation. 1990;81:1680–1687.[Abstract/Free Full Text]
6. Jiang CW, Sarrel PM, Lindsay DC, Poole-Wilson PA, Collins P. Endothelium-independent relaxation of rabbit coronary artery by 17 beta-oestradiol in vitro. Br J Pharmacol. 1991;104:1033–1037.[Medline] [Order article via Infotrieve]
7. Gilligan DM, Badar DM, Panza JA, Quyyumi AA, Cannon RR. Acute vascular effects of estrogen in postmenopausal women. Circulation. 1994;90:786–791.[Abstract/Free Full Text]
8. McCrohon JA, Adams MR, McCredie RJ, Robinson J, Pike A, Abbey M, Keech AC, Celermajer DS. Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women. Clin Endocrinol. 1996;45:435–441.[Medline] [Order article via Infotrieve]
9. Rajkumar C, Kingwell BA, Cameron JD, Waddel T, Mehra R, Christophidis N, Komesaroff PA, McGrath B, Jennings GL, Sudhir K, Dart AM. Hormonal therapy increases arterial compliance in postmenopausal women. J Am Coll Cardiol. 1997;30:350–356.[Abstract]
10. New G, Timmins KL, Duffy SJ, Tran BT, O'Brien RC, Harper RW, Meredith IT. Long-term estrogen therapy improves vascular function in male to female transsexuals. J Am Coll Cardiol. 1997;29:1437–1444.[Abstract]
11. McCrohon JA, Walters WA, Robinson JT, McCredie RJ, Turner L, Adams MR, Handelsman DJ, Celermajer DS. Arterial reactivity is enhanced in genetic males taking high dose estrogens. J Am Coll Cardiol. 1997;29:1432–1436.[Abstract]
12. Rosano GM, Sarrel PM, Poole-Wilson PA, Collins P. Beneficial effect of oestrogen on exercise-induced myocardial ischaemia in women with coronary artery disease. Lancet. 1993;342:133–136.[Medline] [Order article via Infotrieve]
13. Willekes C, Hoogland HJ, Keizer HA, Hoeks AP, Reneman RS. Female sex hormones do not influence arterial wall properties during the normal menstrual cycle. Clin Sci. 1997;92:487–491.[Medline] [Order article via Infotrieve]
14. Karpanou EA, Vyssoulis GP, Papakyriakou SA, Toutouza MG, Toutouzas PK. Effects of menopause on aortic root function in hypertensive women. J Am Coll Cardiol. 1996;28:1562–1566.[Abstract]
15. Gangar KF, Vyas S, Whitehead M, Crook D, Meire H, Campbell S. Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause. Lancet. 1991;338:839–842.[Medline] [Order article via Infotrieve]
16. Pines A, Fisman EZ, Drory Y, Levo Y, Shemesh J, Ben-Ari E, Ayalon D. Menopause-induced changes in Doppler-derived parameters of aortic flow in healthy women. Am J Cardiol. 1992;69:1104–1106.[Medline] [Order article via Infotrieve]
17. Hoeks AP, Brands PJ, Smeets FA, Reneman RS. Assessment of the distensibility of superficial arteries. Ultrasound Med Biol. 1990;16:121–128.[Medline] [Order article via Infotrieve]
18. Kool MJ, van Merode T, Reneman RS, Hoeks AP, Struyker Boudier HA, Van Bortel LM. Evaluation of reproducibility of a vessel wall movement detector system for assessment of large artery properties. Cardiovasc Res. 1994;28:610–614.[Abstract/Free Full Text]
19. Riley WA, Evans GW, Sharrett AR, Burke GL, Barnes RW. Variation of common carotid artery elasticity with intimal-medial thickness: the ARIC Study. Ultrasound Med Biol. 1997;23:157–164.[Medline] [Order article via Infotrieve]
20. Evans GW, Riley WA, Arnett DK, Barnes RW, Burke GL. Analysis of ratio's: a case study based on arterial distensibility. Control Clin Trials. 1993;14:447.
21. Firebaugh G, Gibbs JP. User's guide to ratio variables. Am Sociol Rev. 1985;50:713–722.
22. Reneman RS, van Merode T, Brands PJ, Hoeks AP. Inhomogeneities in arterial wall properties under normal and pathological conditions. J Hypertens. 1992;10(suppl):S35–S39.
23. Nichols WW, O'Rourke MF. McDonald's Blood Flow in Arteries. 3rd ed. London, UK: Edward Arnold, 1990.
24. Laogun AA, Gosling RG. In vivo arterial compliance in man. Clin Phys Physiol Meas. 1982;3:201–212.[Medline] [Order article via Infotrieve]
25. London GM, Guerin AP, Pannier B, Marchais SJ, Stimpel M. Influence of sex on arterial hemodynamics and blood pressure: role of body height. Hypertension. 1995;26:514–519.[Abstract/Free Full Text]
26. Riley WA, Barnes RW, Evans GW, Burke GL. Ultrasonic measurement of the elastic modulus of the common carotid artery: the Atherosclerosis Risk in Communities (ARIC) Study. Stroke. 1992;23:952–956.[Abstract/Free Full Text]
27. Hansen F, Mangell P, Sonesson B, Lanne T. Diameter and compliance in the human common carotid artery–variations with age and sex. Ultrasound Med Biol. 1995;21:1–9.[Medline] [Order article via Infotrieve]
28. Taquet A, Bonithon-Kopp C, Simon A, Levenson J, Scarabin Y, Malmejac A, Ducimetiere P, Guize L. Relations of cardiovascular risk factors to aortic pulse wave velocity in asymptomatic middle-aged women. Eur J Epidemiol. 1993;9:298–306.[Medline] [Order article via Infotrieve]
29. Losordo DW, Kearney M, Kim EA, Jekanowski J, Isner JM. Variable expression of the estrogen receptor in normal and atherosclerotic coronary arteries of premenopausal women. Circulation. 1994;89:1501–1510.[Abstract/Free Full Text]
30. Karas RH, Patterson BL, Mendelsohn ME. Human vascular smooth muscle cells contain functional estrogen receptor. Circulation. 1994;89:1943–1950.[Abstract/Free Full Text]
31. Riedel M, Rafflenbeul W, Lichtlen P. Ovarian sex steroids and atherosclerosis. Clin Invest. 1993;71:406–412.[Medline] [Order article via Infotrieve]
32. Beldekas JC, Smith B, Gerstenfeld LC, Sonenshein GE, Franzblau C. Effects of 17 beta-estradiol on the biosynthesis of collagen in cultured bovine aortic smooth muscle cells. Biochemistry. 1981;20:2162–2167.[Medline] [Order article via Infotrieve]
33. Fischer GM, Swain ML. Effects of estradiol and progesterone on the increased synthesis of collagen in atherosclerotic rabbit aortas. Atherosclerosis. 1985;54:177–185.[Medline] [Order article via Infotrieve]
34. Toda T, Tsuda N, Nishimori I, Leszczynski DE, Kummerow FA. Morphometrical analysis of the aging process in human arteries and aorta. Acta Anat. 1980;106:35–44.[Medline] [Order article via Infotrieve]
35. Arnett DK, Evans GW, Riley WA. Arterial stiffness: a new cardiovascular risk factor? Am J Epidemiol. 1994;140:669–682.[Free Full Text]
36. Hodes RJ, Lakatta EG, McNeil CT. Another modifiable risk factor for cardiovascular disease? Some evidence points to arterial stiffness. J Am Geriatr Soc. 1995;43:581–582.[Medline] [Order article via Infotrieve]
37. Wada T, Kodaira K, Fujishiro K, Maie K, Tsukiyama E, Fukumoto T, Uchida T, Yamazaki S. Correlation of ultrasound-measured common carotid artery stiffness with pathological findings. Arterioscler Thromb. 1994;14:479–482.[Abstract/Free Full Text]
38. Megnien JL, Simon A, Denarie N, Del-Pino M, Gariepy J, Segond P, Levenson J. Aortic stiffening does not predict coronary and extracoronary atherosclerosis in asymptomatic men at risk for cardiovascular disease. Am J Hypertens. 1998;11:293–301.[Medline] [Order article via Infotrieve]
39. Vaitkevicius PV, Fleg JL, Engel JH, O'Connor FC, Wright JG, Lakatta LE, Yin FC, Lakatta EG. Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation. 1993;88:1456–1462.[Abstract/Free Full Text]
40. Riley WA, Freedman DS, Higgs NA, Barnes RW, Zinkgraf SA, Berenson GS. Decreased arterial elasticity associated with cardiovascular disease risk factors in the young: Bogalusa Heart Study. Arteriosclerosis. 1986;6:378–386.[Abstract/Free Full Text]
41. Alva F, Samaniego V, Gonzalez V, Moguel R, Meaney E. Structural and dynamic changes in the elastic arteries due to arterial hypertension and hypercholesterolemia. Clin Cardiol. 1993;16:614–618.[Medline] [Order article via Infotrieve]
42. Hirai T, Sasayama S, Kawasaki T, Yagi S. Stiffness of systemic arteries in patients with myocardial infarction: a noninvasive method to predict severity of coronary atherosclerosis. Circulation. 1989;80:78–86.[Abstract/Free Full Text]
43. Lehmann ED, Hopkins KD, Jones RL, Rudd AG, Goslings RG. Aortic distensibility in patients with cerebrovascular disease. Clin Sci. 1995;89:247–253.[Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				D. S. Hydock, C.-Y. Lien, C. M. Schneider, and R. Hayward Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3254 - H3264. [Abstract] [Full Text] [PDF]

				R. P. Wildman, L. L. Schott, S. Brockwell, L. H. Kuller, and K. Sutton-Tyrrell A dietary and exercise intervention slows menopause-associated progression of subclinical atherosclerosis as measured by intima-media thickness of the carotid arteries J. Am. Coll. Cardiol., August 4, 2004; 44(3): 579 - 585. [Abstract] [Full Text] [PDF]

				C. W. Myers, W. B. Farquhar, D. E. Forman, T. D. Williams, D. L. Dierks, and J. A. Taylor Carotid distensibility characterized via the isometric exercise pressor response Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2592 - H2598. [Abstract] [Full Text] [PDF]

				S. A. Hope, D. B. Tay, I. T. Meredith, and J. D. Cameron Comparison of generalized and gender-specific transfer functions for the derivation of aortic waveforms Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1150 - H1156. [Abstract] [Full Text] [PDF]

				P. Angerer, W. Kothny, S. Stork, and C. von Schacky Hormone replacement therapy and distensibility of carotid arteries in postmenopausal women: a randomized, controlled trial J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1789 - 1796. [Abstract] [Full Text] [PDF]

				C. S. Hayward, R. P. Kelly, and P. Collins The roles of gender, the menopause and hormone replacement on cardiovascular function Cardiovasc Res, April 1, 2000; 46(1): 28 - 49. [Full Text] [PDF]

				R. S Reneman and A. P.G Hoeks Noninvasive vascular ultrasound: An asset in vascular medicine Cardiovasc Res, January 1, 2000; 45(1): 27 - 35. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Westendorp, I. C. D. Articles by Witteman, J. C. M. Search for Related Content PubMed PubMed Citation Articles by Westendorp, I. C. D. Articles by Witteman, J. C. M. Related Collections Pathophysiology Risk Factors Doppler ultrasound, Transcranial Doppler etc.