Evaluation of Cardiovascular Risk Factors in Women with Uterine Leimyoma: Is There a Link with Atherosclerosis?

Abstract

Objective: Both uterine leimyoma (UL) and cardiovascular disease are public health problems affecting women at different age ranges. Smoking, obesity, and hypertension have been shown to be associated with UL in different random studies. However cardiovascular risk factors have not been evaluated systematically in patients with UL. Accordingly, we aimed to evaluate the cardiovascular risk factors and their relation with the presence of UL. Material and Methods: One hundred and eighty nine patients with the pathological diagnosis of UL and one hundred and eighty nine age matched control subjects without UL were retrospectively included in the study from our data base of the pathology and gynecology departments. Controls were patients with intact uteri who had visited the same physicians for a routine checkup that included a pelvic examination and uterine sonogram and without mention of physical findings consistent with UL. The following clinical and demographic parameters were recorded; age, sex, hypertension, diabetes mellitus, and hypercholesterolemia. Current cigarette smoking was defined as active smoking within the past 12 months. Results: Comparison of cardiovascular risk factors between with and without UL revealed that the presence of hypertension (80 (42.3%) vs 53 (28%) p=0.004) diabetes mellitus (33 (17.4%) vs. 16 (8.4%) p=0.009), smoking (31 (16.4%) vs. 11 (5.8%) p=0.001), were significantly higher in patients with UL than in control subjects. The mean-age and presence of hyperlipidemia were comparable between the two groups. Logistic regression analysis revealed an independent and positive association of UL with the presence of hypertension (odds ratio 2.02 CI: 1.25-3.27 p=0.004), diabetes mellitus (odds ratio 2.43 CI: 1.23-4.79 p=0.010), and smoking status (odds ratio 3.46 CI: 1.65-7.22 p=0.001). Conclusion: We have shown that major cardiovascular risk factors namely, hypertension, diabetes mellitus and smoking are significantly and independently associated with UL. Our findings highlight the possible association of UL with atherosclerosis. Turkish Anahtar Kelimeler: Ateroskleroz, kardiyovasküler risk faktörleri, hipertansiyon, diabetes mellitus, sigara içme, uterus leyomiyomu Amaç: Uterus leiomyomu (UL) ve kardiyovasküler hastalıklar kadınları değişik yaşlarda etkileyen halk sağlığı problemleridir. Farklı çalışmalarda sigara, obezite ve hipertansiyonun UL ile ilişkisi gösterilmiştir. Buna karşın, UL olanlarda kardiyovasküler risk faktörleri sistematik olarak değerlendirilmemiştir. Bu doğrultuda, kardiyovasküler risk faktörleri ve bunların UL varlığı ile ilişkisini araştırmayı hedefledik. Hastalar ve Metodlar: Patoloji ve jinekoloji bölümlerinin veri tabanında kayıtlı UL tanısı almış 189 hasta ve yaş bakımından eşleştirilmiş UL bulunmayan 189 kontrol vakası retrospektif olarak incelendi. Kontrol hastaları rutin check-up amacıyla aynı hekimlere başvuran, pelvik muayene ve ultrasonografisiye göre uterusu normal olup, UL fizik bulgusu saptanmayan kişilerden oluştu. Yaş, cinsiyet, hipertansiyon, diabetes mellitus ve hiperkolesterolemi için klinik ve demografik parametreler kaydedildi. Aktif sigara kullanımı son 12 ayda aktif sigara içmek olarak tanımlandı. Bulgular: UL olan ve olmayan hastalarda kardiyovasküler risk faktörleri kıyaslandığında, hipertansiyon varlığı [80 (42.3%) vs 53 (28%) p=0.004], diabetes mellitus [33 (17.4%) vs 16 (8.4%) p=0.009], sigara kullanımı [31 (16.4%) vs 11 (5.8%) p=0.001] UL olanlarda kontrollere göre anlamlı fazla bulundu. Ortalama yaş ve hiperlipidemi varlığı iki grup arasında benzer saptandı. Lojistik regresyon analizinde UL ile hipertansiyon varlığı (odds oranı 2.02 GA: 1.25-3.27, p=0.004), diabetes mellitus (odds oranı: 2.43, GA: 1.23-4.79, p=0.01) ve sigara kullanımı (odds oranı: 3.46, GA: 1.65-7.22, p=0.001) arasında bağımsız ve pozitif ilişki gösterildi. Sonuç: Majör kardiovasküler risk faktörlerinden hipertansiyon, diabetes mellitus ve sigara kullanımının UL ile belirgin ve bağımsız olarak ilişkili olduğunu saptadık. Sonuçlarımız UL ile ateroskleroz olası ilişkisine ışık tutabilir.

Keywords

• Atherosclerosis, cardiovascular risk factors, hypertension, diabetes mellitus, smoking, uterine leimyomata (UL)

Evaluation of Cardiovascular Risk Factors in Women with Uterine Leimyoma: Is There a Link with Atherosclerosis?

Öz

References

1. Ross RK, Pike MC, Vessey MP, Bull D, Yeates D, Casagrande JT. Risk factors for uterine fibroids: reduced risk associated with oral contraceptives. Br Med J 1986;293:359-62. [CrossRef]
2. Vollenhoven B. Introduction: the epidemiology of uterine leiomyo mas. Baillieres Clin Obstet Gynaecol 1998;12:169-76. [CrossRef]
3. Newbold RR, DiAugustine RP, Risinger JI, Everitt JI, Walmer DK, Parrott EC, et al. Advances in uterine leiomyoma research: con ference overview, summary, and future research recommenda tions. Environ Health Perspect 2000;108:769-73. [CrossRef]
4. Cramer SF, Horiszny JA, Leppert P Epidemiology of uter ine leiomyomas. With an etiologic hypothesis. J Reprod Med 1995;40:595-600.
5. Schwartz SM, Marshall LM, Baird DD. Epidemiologic contribu tions to understanding the etiology of uterine leiomyomata. En viron Health Perspect 2000;108:821-7. [CrossRef]
6. Day Baird D, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol 2003;188:100-7. [CrossRef]
7. Borgfeldt C, Andolf E. Transvaginal ultrasonographic findings in the uterus and the endometrium: low prevalence of leiomyoma in a random sample of women age 25-40 years. Acta Obstet Gy necol Scand 2000;79:202-7. [CrossRef]
8. Luoto R, Kaprio J, Rutanen EM, Taipale P, Perola M, Koskenvuo M. Heritability and risk factors of uterine fibroids-the Finnish Twin Cohort Study. Maturitas 2000;37:15-26. [CrossRef]

9. Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol 990;94:435-8.
10. Marshall LM, Spiegelman D, Manson JE, Goldman MB, Barbieri RL, Stampfer MJ, et al. Risk of uterine leiomyomata among pre menopausal women in relation to body size and cigarette smok ing. Epidemiology 1998;9:511-7. [CrossRef]
11. Boynton-Jarrett R, Rich-Edwards J, Malspeis S, A. Missmer S, Wright R. A prospective study of hypertension and risk of uterine leiomyomata. Am J Epidemiol 2005;161:628-38. [CrossRef]
12. Hashimoto K, Azuma C, Kamiura S, Kimura T, Nobunaga T, Kanai T, et al. Clonal determination of uterine leiomyomas by analyzing differential inactivation of the X-chromosome-linked phosphoglyc erokinase gene. Gynecol Obstet Invest 1995;40:204-8. [CrossRef]
13. Wise LA, Palmer JR, Stewart EA, Rosenberg L. Age-specific incidence rates for self-reported uterine leiomyomata in the Black Women's Health Study. Obstet Gynaecol 2005;105:563-8. [CrossRef]
14. Kjerulff KH, Langenberg P, Seidman JD, Stolley PD, Guzinski GM. Uterine leiomyomas. Racial differences in severity, symptoms and age of diagnosis. J Reprod Med 1996;41:483-90.
15. Ligon AH, Morton CC. Leiomyomata: heritability and cytogenetic studies. Hum Reprod Update 2001;7:8-14. [CrossRef]
16. Chiaffarino F, Parazzini F, La Vecchia C, Marsico S, Surace M, Ricci E. Use of oral contraceptives and uterine fibroids: results from a case control study. Br J Obstet Gynaecol 1999;106:857-60. [CrossRef]
17. Lumbiganon P, Rugpao S, Phandhu-fung S, Laopaiboon M, Vudhikam raksa N, Werawatakul Y. Protective effect of depotedroxyprogesterone acetate on surgically treated uterine leiomyomas: a multicentre case control study. Br J Obstet Gynaecol 1996;103:909-14. [CrossRef]
18. Faerstein E, Szklo M, Rosenshein N. Risk factors for uterine leio myoma: a practice-based case-control study I. African American heritage, reproductive history, body size, and smoking. Am J Epi demiol 2001;153:1-10. [CrossRef]
19. Okoronkwo MO. Body weight and uterine leiomyomas among women in Nigeria. West Afr J Med 1999;18:52-4.
20. Sato F, Nishi M, Kudo R, Miyake H. Body fat distribution and uter ine leiomyomas. J Epidemiol 1998;8:176-80. [CrossRef]
21. Silver MA., Raghuvir R, Fedirko B, Esler D. Systemic hypertension among women with uterine leiomyomata: potential final com mon pathways of target end-organ remodeling. J Clin Hypertens (Greenwich) 2005;7:664-8. [CrossRef]
22. Kawano H, Do YS, Kawano Y, Starnes V, Barr M, Law RE, et al. Angiotensin II has multiple profibrotic effects in human cardiac fibroblast. Circulation 2000;101:1130-7. [CrossRef]
23. Itoh H, Mukoyama M, Pratt RE, Gibbons GH, Dzau VJ. Multiple autocrine growth factors modulate vascular smooth muscle cell growth response to angiotensin II. J Clin Invest 1993;91:2268-74. [CrossRef]
24. Baker KM, Booz GW, Dostal DE. Cardiac actions of angiotensin II: role of intracardiac renin angiotensin system. Annu Rev Physiol 1992;54:227-41. [CrossRef]
25. Brandon DD, Bethea CL, Strawn EY, Novy MJ, Burry KA, Har rington MS, et al. Progesterone receptor messenger ribonucleic acid and protein are overexpressed in human uterine leiomyo mas. Am J Obstet Gynecol 1993;169:78-85.
26. Dou Q, Zhao Y, Tarnuzzer RW, Rong H, Williams RS, Schultz GS, et al. Suppression of transforming growth factor-beta (TGF beta) and TGF beta receptor messenger ribonucleic acid and protein expression in leiomyomata in women receiving gonadotropin releasing hormone agonist therapy. J Clin Endocrinol Metab 1996;81:3222-30. [CrossRef]
27. Wagenknecht LE, Zaccaro D, Espeland MA, Karter AJ, O'Leary DH, Haffner SM. Diabetes and progression of carotid athero sclerosis: the insulin resistance atherosclerosis study. Arterioscler Thromb Vasc Biol 2003;23:1035-41. [CrossRef]
28. Rajaram V, Pandhya S, Patel S, Meyer PM, Goldin M, Feinstein MJ, Neems R, Liebson PR, Fiedler BM, Macioch JE, Feinstein SB. Role of surrogate markers in assessing patients with diabetes mellitus and the metabolic syndrome and in evaluating lipid-low ering therapy. Am J Cardiol 2004;93(11A):32C-48C. [CrossRef]
29. Kornowski R, Mintz GS, Lansky J, Hong MK, Kent KM, Pichard AD, et al. Paradoxic decreases in atherosclerotic plaque mass in insulin treated diabetic patients. Am J Cardiol 1998;81:1298-304. [CrossRef]
30. Vavuranakis M, Stefanadis C, Toutouzas K, Pitsavos C, Spanos V, Toutouzas P. Impaired compensatory coronary artery enlarge ment in atherosclerosis contributes to the development of coro nary artery stenosis in diabetic patients. An in vivo intravascular ultrasound study. Eur Heart J 1997;18:1090-4. [CrossRef]
31. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607. [CrossRef]
32. Yam D. Insulin-cancer relationships: possible dietary implication. Med Hypotheses 1992;38:111-7. [CrossRef]
33. Bornfeldt KE, Arnqvist HJ, Capron L. In vivo proliferation of rat vascular smooth muscle in relation to diabetes mellitus, insulinlike growth factor I and insulin. Diabetologia 1992;35:104-8. [CrossRef]
34. Cramer SF, Robertson AL Jr, Ziats NP, Pearson OH. Growth po tential of human uterine leiomyomas: some in vitro observations and their implications. Obstet Gynecol 1985;66:36-41.
35. Poretsky L, Galin MF. The gonadotropic function of insulin. En docr Rev 1987;8:132-41. [CrossRef]
36. Samadi AR, Lee NC, Flanders WD, Boring JR 3rd, Parris EB. Risk factors for selfreported uterine fibroids: a case-control study. Am J Public Health 1996;86:858-62. [CrossRef]
37. Parazzini F, Negri E, La Vecchia C, Rabaiotti M, Luchini L, Villa A, et al. Uterine myomas and smoking. Results from an Italian study. J Reprod Med 1996;41:316-20.
38. Baron JA, La Vecchia C, Levi F. The antiestrogenic effect of ciga rette smoking in women. Am J Obstet Gynecol 1990;162:502-14.
39. Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Dia betes Study (UKPDS:23). BMJ 1998;316:823-8. [CrossRef]
40. Adler AI, Stevens RJ, Neil A, Stratton IM, Boulton AJ, Holman RR. UKPDS 59: Hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes. Diabe tes Care 2002;25:894-99. [CrossRef]
41. Li JM, Cui TX, Shiuchi T, Liu HW, Min LJ, Okumura M, et al. Nico tine enhances angiotensin II-induced mitogenic response in vas cular smooth muscle cells and fibroblasts. Arterioscler Thromb Vasc Biol 2004;24:80-4. [CrossRef]
42. Mashal RD, Fejzo ML, Friedman AJ, Mitchner N, Nowak RA, Rein MS, et al. Analysis of androgen receptor DNA reveals the inde pendent clonal origins of uterine leiomyomata and the secondary nature of cytogenetic aberrations in the development of leiomy omata. Genes Chromosomes Cancer 1994;11:1-6. [CrossRef]
43. Chung IM, Schwartz SM, Murry CE. Clonal architecture of normal and atherosclerotic aorta: implications for atherogenesis and vas cular development. Am J Pathol 1998;152:913-23.
44. Moss NS, Benditt EP. Human atherosclerotic plaque cells and leiomyoma cells. Comparison of in vitro growth characteristics. Am J Pathol 1975;78:175-90.