Heart Vessels (2006) 21:38–41 DOI 10.1007/s00380-005-0872-2

© Springer-Verlag 2006

ORIGINAL ARTICLE Rifat Eralp Ulusoy · Ergun Demiralp · Ata Kirilmaz Fethi Kilicaslan · Namik Ozmen · Nezihi Kucukarslan Ejder Kardesoglu · Levent Tutuncu · Ozcan Keskin Bekir Sitki Cebeci

Aortic elastic properties in young pregnant women

Received: December 3, 2004 / Accepted: October 7, 2005

Abstract This study aimed to investigate the aortic elastic properties of young pregnant women by comparing them with those of age-matched healthy females. The study group consisted of 21 pregnant women at a mean age of 26 ± 1 years; 22 healthy women at a mean age of 25 ± 1 years constituted the control group. Doppler-color echocardiographic variables and serum estradiol (E2) levels were measured from both groups. The blood samples were obtained from the control group in the first week after menstrual bleeding. Diastolic and systolic blood pressure (DBP and SBP, respectively) were measured with a sphygmomanometer. Systolic and diastolic aortic diameters (AOS and AOD, respectively) were measured 3 cm proximal to the aortic valves. Aortic elastic properties were assessed according to the following formulas: 1, Aortic strain = (AOS AOD)/AOD; 2, Aortic distensibility = 2 ¥ (AOS - AOD)/ (PP ¥ AOD); 3, Aortic diameter change = AOS - AOD; 4, Aortic stiffness index = ln(SBP/DBP)/(AOS - AOD)/ R.E. Ulusoy1 (*) · E. Demiralp · A. Kirilmaz · F. Kilicaslan · N. Ozmen · E. Kardesoglu · B.S. Cebeci Department of Cardiology, Gata Haydarpasa Military Teaching Hospital, Istanbul, Turkey N. Kucukarslan Department of Cardiovascular Surgery, Gata Haydarpasa Military Teaching Hospital, Istanbul, Turkey L. Tutuncu Department of Obstetrics and Gynecology, Gata Haydarpasa Military Teaching Hospital, Istanbul, Turkey O. Keskin Department of Emergency, Gata Haydarpasa Military Teaching Hospital, Istanbul, Turkey Correspondence address: 1 Gulhane Askeri Tip Akademisi Haydarpasa Egitim Hastanesi, Kardiyoloji Servisi, Selimiye Mah. Tibbiye Cad., 34670 Kadikoy, Istanbul, Turkey Tel. +90-216-542-2418; Fax +90-216-348-7880 e-mail: [email protected] This study was presented as an oral presentation at the XXth Turkish Society of Cardiology Meeting (November 27–30, 2004) in Antalya, Turkey

AOD. The results were expressed as mean ± standard deviation and compared by t-test between groups. P < 0.05 was considered as statistically significant. All women in the study group were in their first pregnancy and second trimester. The height and weight were 160 ± 5 vs 164 ± 6 cm and 60 ± 9 vs 54 ± 3 kg in the study vs control groups, respectively (P < 0.05). The AOD was 26 ± 3 vs 26 ± 4 mm and AOS 29 ± 3 vs 28 ± 4 mm. Pulse pressure was 43 ± 3 vs 45 ± 8 mmHg in the study vs control groups, respectively (P > 0.05). The serum E2 level was significantly higher in pregnant women (21 300 ± 2 300 pg/ml). Derived aortic elastic properties in pregnant women were also increased significantly (P < 0.0005). The indexes of aortic elastic properties are altered and aortic stiffness is decreased among young pregnant women. This may be due to the adaptation mechanisms including high estradiol levels detected in pregnancy. Key words Aortic elastic properties · Pregnancy · Arterial elasticity

Introduction It is generally accepted that a normal pregnancy is characterized by a large increase in total blood volume and in cardiac output.1–3 Blood volume expansion rises up to 50% during the early pregnancy period and the highest increase is reached halfway through gestation. This increased volume needs vascular adaptation in terms of the continuity of cardiac output and circulation. The aorta functions not only as a conduit delivering arterial blood to the tissues, but also as an important modulator of the entire cardiovascular system, buffering the intermittent pulsatile output from the heart to provide steady flow to capillary beds. The manifestations and physiologic implications of this pulsatility in the vascular system are of considerable interest, because it provides useful information regarding the function of large arteries and systemic vasculature vasomotion.4,5 Additionally, 48% of women under the age of 40 years who have an acute dissecting aortic aneurysm are pregnant.6 The most

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frequent localization of dissection is the ascending aorta (De Bakey types I and II). The prognosis of this disease in the mother is generally catastrophic, and 94% of cases die within the first 48 h.6 To the best of our knowledge, the elastic properties of the aorta have never been reported in young pregnant women. In this study, our aim was to evaluate the elastic properties of the aorta in young pregnant women, and to find out the effects of pregnancy on aortic elastic properties.

Materials and methods The study included 21 white pregnant women (study group, mean age 26 ± 1 years), who were admitted to our obstetrical outpatient clinic. Twenty-two age-matched, healthy women constituted the control group (mean age 25 ± 1 years). Only nonsmokers in both groups were included in the study. Blood pressure measurement Diastolic and systolic blood pressures (DBP and SBP, respectively) were measured in a silent room with a mercury cuff sphygmomanometer from right arm after 10 min of rest following echocardiographic examination. The first and the fifth Koratkoff sounds were taken for the SBP and DBP, respectively. Coffee, tea, other types of beverages, or cigarettes were not used or ingested from half an hour before the blood pressure measurements. The average of three consecutive measurements was accepted as the blood pressure measurement. Pulse pressure (PP) was defined as the difference of systolic and diastolic blood pressures. Serum estradiol measurement Serum estradiol (E2) levels were assessed from the venous blood obtained from both groups. The blood samples from the control group were drawn and assessed in the first week after the completion of menstrual bleeding. Serum concentrations of E2 were determined with the use of a radioimmunoassay method and Coat-A-Count E2 kit (Coat-A-Count estradiol kit; Diagnostic Products, Los Angeles, CA, USA). The intra-assay coefficient of variation was 5.6% and the lowest limit of detection was 8 pg/ml. Assays were performed by the laboratory technicians blinded to both groups. Echocardiographic measurement All cases underwent a complete two-dimensional transthoracic echocardiographic and Doppler study in the left lateral decubitus position from multiple windows. The echocardiographic studies of the control group were completed within their first week after the menstrual bleeding. All studies were performed with Vingmed system V (GE,

Horten, Norway) echocardiograph using a 2.5-MHz transducer. Echocardiographic measurements were performed according to the recommendations of the American Society of Echocardiography.7 Left ventricular dimensions were obtained using the parasternal short-axis view at the level of the papillary muscle. M-mode measurements were obtained using the leading-edge technique in accordance with recommendations as previously described. Gain, depth, and sector angles were individualized for best measurement. In each echocardiographic method, M-mode traces were recorded at a speed of 50 mm/s and the Doppler signals at 100 mm/s, and measurements of at least three cardiac cycles were averaged in sinus rhythm. Systolic and diastolic aortic diameters (AOS and AOD, respectively) were measured from 3 cm proximal to the aortic valves as previously described.8,9 Echocardiograms were read offline with an interobserver reproducibility of 90%.

Indexes of aortic elastic properties Aortic elastic properties were derived from the measurements obtained from the M-mode recordings and blood pressure in both groups and were expressed as follows: 1. Aortic strain = (AOS - AOD)/AOD 2. Aortic distensibility (cm2/dyn) = 2 ¥ (AOS - AOD)/(PP ¥ AOD) 3. Aortic diameter change (mm) = AOS - AOD 4. Aortic stiffness index = ln(SBP/DBP)/(AOS - AOD)/ AOD7,8 Statistical analysis Variables were summarized by standard descriptive statistics and expressed as mean ± SD. Categorical and continuous variables were compared using the chi-square test and the t-test (Mann–Whitney U-test when Levene test is significant), respectively. A P value of less than 0.05 was considered statistically significant.

Results Table 1 summarizes the demographic properties of the cases. There was no significant difference between the groups with respect to age. All women in the study group were within their first pregnancy and in their second trimester. The height and weight were 160 ± 5 vs 164 ± 6 cm (P = 0.028) and 60 ± 9 vs 54 ± 3 kg (P = 0.004) in the study and control groups, respectively. Although the heart rate in pregnant women was higher than those of the control subjects, it did not reach a statistically significant level. The serum level of the E2 in pregnant women was 21 300 ± 2 300 pg/ml compared with 215 ± 43 pg/ml in the control group (P < 0.05). The E2 serum level was significantly correlated for both groups with the aortic elastic properties (P < 0.0005). Correlation coefficient between E2 and aortic

40 Table 1. Comparison of demographics between pregnant and control groups Variable

Study group (n = 21)

Control group (n = 22)

P

Age (years) Height (cm) Weight (kg) Heart rate (beats/min) BSA (m2) Estradiol (pg/ml)

26 ± 1 160 ± 5 60 ± 9 85 ± 11 1.6 ± 0.13 21300 ± 2300

25 ± 1 164 ± 6 54 ± 3 81 ± 14 1.6 ± 0.06 215 ± 43

NS 0.028 0.004 NS NS <0.0005

BSA, body surface area; NS, not significant

Table 2. Comparison of aortic elastic property measurements between the study and control groups Variable

Study group (n = 21)

Control group (n = 22)

P

AOD (mm) AOS (mm) PP (mmHg) Aortic strain Aortic distensibility (cm2/dyn) Aortic diameter change (mm) Aortic stiffness index

26 ± 3 29 ± 3 43 ± 4 0.149 ± 0.034 4.53 ± 1.17 3.75 ± 0.72 11.5 ± 2.6

26 ± 4 28 ± 3 45 ± 8 0.093 ± 0.037 2.72 ± 1.08 2.3 ± 0.73 21.7 ± 9.0

NS NS NS <0.0005 <0.0005 <0.0005 <0.0005

AOD, aortic diameter in diastole; AOS, aortic diameter in systole; PP, pulse pressure

strain, aortic distention, aortic diameter change, and aortic stiffness index was 0.63, 0.87, 0.87, and -0.60 in the pregnant group and 0.79, 0.76, 0.91, and 0.79 in the control group, respectively (P < 0.05). Among the indexes of aortic elastic properties, aortic strain, aortic distensibility, and aortic diameter change were significantly higher than those of the control group. The aortic stiffness index was significantly decreased in pregnant women when compared with control group values (Table 2). Comparison of aortic elastic properties indexed to the heart rate between groups revealed the same results.

Discussion The present study has clearly shown that the indexes of aortic elastic properties are altered and aortic stiffness is decreased among young pregnant women. The significant difference in height and weight between groups can be attributed to the hemodynamic effects of pregnancy, including weight gain and volume overload. The aortic elastic parameters were derived from the pulsatile change in diameter of the ascending aorta, and from the conventional right brachial artery systolic and diastolic pressures. These noninvasive measurements have been confirmed as the determinants of aortic distensibility, with a high degree of accuracy in comparison with invasive means.9,10 By selecting the young pregnant women for this study, the effects of the aging process and of the atherosclerosis on the aortic elastic properties were minimized. The main difference between the pregnant women and control subjects was the level of E2. Pregnant women have an approximately 100 times higher E2 concentration than

that of control subjects. Although this may be mechanistically or directly responsible for the increased elasticity of the aorta in pregnancy, the study design does not elucidate the mechanism. Normal pregnancy is characterized by a 50% increase in total blood volume and in cardiac output, which requires vascular adaptation in terms of the continuity of cardiac output and circulation. Aortic distensibility and compliance have been reported to be significantly increased during normal pregnancy in rats.11 The aorta functions not only as a conduit delivering arterial blood to the tissues, but also as an important modulator of the entire cardiovascular system, buffering the intermittent pulsatile output from the heart to provide steady flow to capillary beds. There is a relationship between heart rate and aortic elasticity. The slight increase in heart rate in pregnant women can be attributed to normal physiologic response to the pregnancy. There was no correlation between heart rate and aortic elasticity properties in both groups. Previous studies reported that estrogen therapy has a beneficial effect both on endothelial function and aortic distensibility on postmenopausal women, probably via estrogen receptors located in the aortic tissue.12–14 Additionally, estrogen modulates catecholamine release, endothelium-derived relaxing factor, calcium channels, and membrane polarization, causing increased blood supply to the epicardial coronary arteries and to the vasa vasorum of the aortic wall.13,16–21 These studies indirectly support our results, which may substitute a mechanistic explanation. The adaptation of the cardiovascular system to many physiologic workloads can be achieved with an increase in distensibility, indicating an intrinsic change in the aortic wall, probably by high estrogen blood level and compensation of the elevated blood volume and cardiac output.22 They all

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can participate interactively in the buffering mechanisms during pregnancy. The relation between these mechanisms and the increased incidence of aortic dissection during pregnancy is unclear. In conclusion, the indexes of aortic elastic properties are altered and aortic stiffness is decreased among young pregnant women. This increase may be due to a buffering mechanism of increased estrogen and hemodynamic adaptation in pregnancy. The exact mechanisms involving the increased aortic distensibility during normal pregnancy require further clinical investigation.

References 1. Metcalfe J, McAnulty JH, Ueland K (1994) Cardiovascular physiology. Clin Obstet Gynecol 9:619–626 2. Metcalfe J, McAnulty JH, Ueland K (1986) Haemodynamics in pregnancy. In: Burwell CS, Metcalfe J (eds) Heart disease and pregnancy: physiology and management. Little, Brown, Boston, pp 11–54 3. Van Oppen AC, Stigter RH, Bruinse HW (1996) Cardiac output in normal pregnancy: a critical review. Obstet Gynecol 87:310–318 4. Stefanadis C, Dernellis J, Vlachopoulos C, Tsioufis C, Tsiamis E, Toutouzas K, Pitsavos C, Toutouzas P (1997) Aortic function in arterial hypertension determined by pressure-diameter relation: effects of diltiazem. Circulation 96:1853–1858 5. Stefanadinis C, Dernellis J, Vavuranakis M, Tsiamis E, Vlachopoulos C, Toutouzas K, Diamandopoulos L, Pitsavos C, Toutouzas P (1998) Effects of ventricular pacing-induced tachycardia on aortic mechanics in man. Cardiovasc Res 39:506–514 6. Monnier JC, Stankowiak C, Dognin C, Bassery-Boulic F (1981) Dissecting aortic aneurysm in the 8th month of a twin pregnancy. A review of the literature. J Gynecol Obstet Biol Reprod (Paris) 10:813–822 7. Henry WL, De Maria A, Gramiak R, King DL, Kisslo JA, Popp RL, Sahn DJ, Schiller NB, Tajik A, Teicholz LE, Weyman AE (1980) Report of the American Society of Echocardiography Committee on nomenclature and standards in two-dimensional echocardiography. Circulation 62:212–217

8. Gorgulu S, Uslu N, Eren M, Celik S, Yildirim A, Dagdeviren B, Tezel T (2003) Aortic stiffness in patients with cardiac syndrome X. Acta Cardiol 58:507–511 9. Stefanadis C, Dernellis J, Toutouzas P (1999) Mechanical properties of the aorta determined by the pressure-diameter relation. Pathol Biol (Paris) 47:696–704 10. Stefanadis C, Stratos C, Boudoulas, H, Kourouklis C, Toutouzas P (1990) Distensibility of the ascending aorta: comparison of invasive and non-invasive techniques in healthy men and in men with coronary artery disease. Eur Heart J 11:990–996 11. Slangen BFM, van Ingen Schenau DS, van Gorp AW, de Mey JGR, Peeters LLH (1997) Aortic distensibility and compliance in conscious pregnant rats. Am J Physiol 272:1260–1265 12. Shores J, Berger KR, Murphy EA, Pyeritz RE (1994) Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan’s syndrome. N Engl J Med 330:1335–1341 13. Toutouzas P (1999) Diseases of the aorta: Medical treatment of the aorta II. Cardiol Clin 17:717–737 14. Lin AL, Gonzalez RJR, Carey KD, Shain SA (1986) Estradiol17beta affects estrogen receptor distribution and elevates progesterone receptor content in baboon aorta. Arteriosclerosis 6:495– 504 15. Polderman KH, Stehouwer CDA, van Kamp GJ, Dekker GA, Verheugt FW, Gooren LJ (1993) Influence of sex hormones on plasma endothelin levels. Ann Intern Med 118:429–432 16. Sarrel PM (1990) Ovarian hormones and the circulation. Maturitas 12:287–298 17. Edouard DA, Pannier BM, London GM, Cuche JL, Safar ME (1998) Venous and arterial behaviour during normal pregnancy. Am J Physiol 274:1605–1612 18. Stefanadis C, Vlachopoulos C, Karayannacos P, Boudoulas H, Stratos C, Filippides T, Agapitos M, Toutouzas P (1995) Effect of vasa vasorum flow on structure and function of the aorta in experimental animals. Circulation 91:2669–2678 19. Karpanou EA, Vyssoulis GP, Papakyriakou SA, Toutouzas MG, Toutouzas P (1996) Effects of menopause on aortic root function in hypertensive women. J Am Coll Cardiol 28:1562–1566 20. Stefanadis C, Wooley CF, Bush CA, Kolibash AJ, Boudoulas H (1998) Aortic distensibility in post-stenotic aortic dilatation: the effect of co-existing coronary artery disease. J Cardiol 18:189–195 21. Gorgulu S, Eren M, Celik S, Dagdeviren B, Uslu N, Suer N, Tezel T (2003) The effects of hormonal therapy on aortic stiffness and left ventricular diastolic function. Acta Cardiol 58:1–8 22. Kasikcioglu E, Oflaz H, Akhan H, Kayserilioglu A, Mercanoglu F, Umman B, Bugra Z (2004) Left ventricular remodeling and aortic distensibility in elite power athletes. Heart Vessels 19:183–188