Opiate exposure increases arterial stiffness, advances vascular age and is an independent cardiovascular risk factor in females: A cross-sectional clinical study

Abstract

Background: Whilst several studies have demonstrated poor cardiovascular health in opiate dependence, its role as a cardiovascular risk factor has not been considered. Methods: Pulse wave analysis was undertaken by radial arterial tonometry (SphygmoCor) in female control and opiate-dependent patients and compared to lifetime opiate use. Results: 222 opiate dependent women were compared to 175 controls. Opiate dependent patients were receiving treatment with buprenorphine (83.3%), methadone (13.5%), or naltrexone (3.2%). Non log transformed chronologic age (CA) for the two groups was 33.58 ± 0.57 (opiate) vs. 32.62 ± 0.96 (controls) years (mean ± S.E.M.; P = 0.39). Vascular Reference Age (RA) 39.30 ± 1.28, vs. 35.03 ± 1.41 the RA-CA difference (5.73 ± 1.02 vs. 2.41 ± 0.91) and the RA/CA ratio (1.16 ± 0.03 vs. 1.07 ± 0.02; all P < 0.02), and all measurements of central arterial stiffness (P < 0.02) were significantly worse for opiates compared to controls. When adjusted for CA, RA and central augmentation pressure and index were all worse by themselves and in interaction with CA (all P < 0.005). At 60 years the modelled RA’s were 83.79 and 67.52 years respectively. The opiate dose-duration interaction showed a dose-response effect with RA (P = 0.0033). After full adjustment for established cardiovascular risk factors, the dose-duration interaction remained significant (P = 10-6), was included in 10 other terms, and dose or duration was included in 15 other interactions. Conclusion: These data show that lifetime opiate use is significantly associated with increased arterial stiffness and vascular age and suggest a dose-response relationship. This relationship is robust and persists after full multivariate adjustment. These findings carry far-reaching implications for opiate-induced generalized acceleration of organismal ageing.

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Reece, A. and Hulse, G. (2013) Opiate exposure increases arterial stiffness, advances vascular age and is an independent cardiovascular risk factor in females: A cross-sectional clinical study. World Journal of Cardiovascular Diseases, 3, 361-370. doi: 10.4236/wjcd.2013.35056.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Jamison, R.N., Serraillier, J. and Michna, E. (2011) Assessment and treatment of abuse risk in opioid prescribeing for chronic pain. Pain Research and Treatment, 941808.
[2] Drug Abuse Warning Network (DAWN). (2009) Treatment Episode Data Set—Admissions (Teds-A)—Concatenated, 1992 to 2009 (Computer file). Prepared by Synectics for Management Decisions, Incorporated. ICPSR25221-v4.
[3] Darke, S., Degenhardt, L. and Mattick, R. (2007) Mortality amongst illicit drug users: Epidemiology, causes and intervention. Cambridge University Press, Sydney, 2007.
[4] Darke, S., Duflou, J. and Torok, M. (2010) The comparative toxicology and major organ pathology of fatal methadone and heroin toxicity cases. Drug and Alcohol Dependence, 106, 1-6. doi:10.1016/j.drugalcdep.2009.07.014
[5] Oviedo-Joekes, E., Brissette, S., Marsh, D.C., Lauzon, P., Guh, D., Anis, A. and Schechter, M.T. (2009) Diacetylmorphine versus methadone for the treatment of opioid addiction. The New England Journal of Medicine, 361, 777-786. doi:10.1056/NEJMoa0810635
[6] Darke, S., Kaye, S. and Duflou, J. (2006) Systemic disease among cases of fatal opioid toxicity. Addiction, 101, 1299-1305. doi:10.1111/j.1360-0443.2006.01495.x
[7] Degenhardt, L., Randall, D., Hall, W., Law, M., Butler, T. and Burns, L. (2009) Mortality among clients of a statewide opioid pharmacotherapy program over 20 years: Risk factors and lives saved. Drug and Alcohol Dependence, 105, 9-15. doi:10.1016/j.drugalcdep.2009.05.021
[8] Sadeghian, S., Darvish, S., Davoodi, G., Salarifar, M., Mahmoodian, M., Fallah, N. and Karimi, A.A. (2007) The association of opium with coronary artery disease. European Journal of Cardiovascular Prevention & Rehabilitation, 14, 715-717. doi:10.1097/HJR.0b013e328045c4e9
[9] Sadeghian, S., Dowlatshahi, S., Karimi, A. and Tazik, M. (2011) Epidemiology of opium use in 4398 patients admitted for coronary artery bypass graft in Tehran Heart Center. Journal of Cardiothoracic Surgery (Torino), 52, 140-141.
[10] Feero, W.G., Guttmacher, A.E. and McCarthy, M.I. (2010) Genomics, type 2 diabetes, and obesity. New England Journal of Medicine, 363, 2339-2350. doi:10.1056/NEJMra0906948
[11] O’Donnell, C.J. and Nabel, E.G. (2011) Genomics of Cardiovascular Disease. New England Journal of Medicine, 365, 2098-2109. doi:10.1056/NEJMra1105239
[12] Helgadottir, A., Thorleifsson, G., Manolescu, A., Gretarsdottir, S., Blondal, T., Jonasdottir, A., Sigurdsson, A., Baker, A., Palsson, A., Masson, G., et al. (2007) A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science, 316, 1491-1493. doi:10.1126/science.1142842
[13] McPherson, R., Pertsemlidis, A., Kavaslar, N., Stewart, A., Roberts, R., Cox, D.R., Hinds, D.A., Pennacchio, L.A., Tybjaerg-Hansen, A., Folsom, A.R., et al. (2007) A common allele on chromosome 9 associated with coronary heart disease. Science, 316, 1488-1491. doi:10.1126/science.1142447
[14] Pasmant, E., Sabbagh, A., Vidaud, M. and Bieche, I. (2010) ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. The FASEB Journal, 25, 444-448. doi:10.1096/fj.10-172452
[15] Visel, A., Zhu, Y., May, D., Afzal, V., Gong, E., Attanasio, C., Blow, M.J., Cohen, J.C., Rubin, E.M. and Pennacchio, L.A. (2010) Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature, 464, 409-412. doi:10.1038/nature08801
[16] Harismendy, O., Notani, D., Song, X., Rahim, N.G., Tanasa, B., Heintzman, N., Ren, B., Fu, X.D., Topol, E.J., Rosenfeld, M.G. and Frazer, K.A. (2011) 9p21 DNA variants associated with coronary artery disease impair interferon-gamma signalling response. Nature, 470, 264-268. doi:10.1038/nature09753
[17] Bazarov, A.V., Van Sluis, M., Hines, W.C., Bassett, E., Beliveau, A., Campeau, E., Mukhopadhyay, R., Lee, W.J., Melodyev, S., Zaslavsky, Y., et al. (2010) p16INK4a-mediated suppression of telomerase in normal and malignant human breast cells. Aging Cell, 9, 736-746. doi:10.1111/j.1474-9726.2010.00599.x
[18] Coppe, J.P., Rodier, F., Patil, C.K., Freund, A., Desprez, P.Y. and Campisi, J. (2011) Tumor suppressor and aging biomarker p16INK4a induces cellular senescence without the associated inflammatory secretory phenotype. The Journal of Biological Chemistry, 286, 36396-36403. doi:10.1074/jbc.M111.257071
[19] Bhaumik, D., Scott, G.K., Schokrpur, S., Patil, C.K., Orjalo, A.V., Rodier, F., Lithgow, G.J. and Campisi, J. (2009) MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8. Aging (Albany NY), 1, 402-411.
[20] Zagon, I.S. and McLaughlin, P.J. (1977) Morphine and brain growth retardation in the rat. Pharmacology, 15, 276-282. doi:10.1159/000136699
[21] McLaughlin, P.J., Zagon, I.S. and White, W.J. (1978) Perinatal methadone exposure in rats. Effects on body and organ development. Biology of the Neonat, 34, 48-54. doi:10.1159/000241104
[22] Cheng, F., Zagon, I.S., Verderame, M.F. and McLaughlin, P.J. (2007) The opioid growth factor (OGF)-OGF receptor axis uses the p16 pathway to inhibit head and neck cancer. Cancer Research, 67, 10511-10518. doi:10.1158/0008-5472.CAN-07-1922
[23] Cheng, F., McLaughlin, P.J., Verderame, M.F. and Zagon, I.S. (2009) The OGF-OGFr axis utilizes the p16INK4a and p21WAF1/CIP1 pathways to restrict normal cell proliferation. Molecular Biology of the Cell, 20, 319-327. doi:10.1091/mbc.E08-07-0681
[24] Zagon, I.S., Verderame, M.F. and McLaughlin, P.J. (2002) The biology of the opioid growth factor receptor (OGFr). Brain Research Reviews, 38, 351-376. doi:10.1016/S0165-0173(01)00160-6
[25] Chien, K.R. and Karsenty, G. (2005) Longevity and lineages: Toward the integrative biology of degenerative diseases in heart, muscle, and bone. Cell, 120, 533-544. doi:10.1016/j.cell.2005.02.006
[26] Reece, A.S. (2007) Psychosocial and treatment correlates of opiate free success in a clinical review of a naltrexone implant program. Substance Abuse Treatment, Prevention, and Policy, 2, 35-49. doi:10.1186/1747-597X-2-35
[27] Reece, A.S. (2007) Evidence of Accelerated Ageing in Clinical Drug Addiction from Immune, Hepatic and Metabolic Biomarkers. Immunity & Ageing, 4, 6-15. doi:10.1186/1742-4933-4-6
[28] Cooper, O.B., Brown, T.T. and Dobs, A.S. (2003) Opiate drug use: A potential contributor to the endocrine and metabolic complications in human immunodeficiency virus disease. Clinical Infectious Diseases, 37, S132-S136. doi:10.1086/375879
[29] Kolarzyk, E., Pach, D., Wojtowicz, B., Szpanowska-Wohn, A. and Szurkowska, M. (2005) Nutritional status of the opiate dependent persons after 4 years of methadone maintenance treatment. Przegl Lek, 62, 373-377.
[30] Rosen, D., Smith, M.L. and Reynolds, C.F. (2008) The prevalence of mental and physical health disorders among older methadone patients. The American Journal of Geriatric Psychiatry, 16, 488-497. doi:10.1097/JGP.0b013e31816ff35a
[31] Hser, Y.I., Gelberg, L., Hoffman, V., Grella, C.E., McCarthy, W. and Anglin, M.D. (2004) Health conditions among aging narcotics addicts: Medical examination results. Journal of Behavioral Medicine, 27, 607-622. doi:10.1007/s10865-004-0005-x
[32] Ceriello, A., Giugliano, D., Passariello, N., Quatraro, A., Dello Russo, P., Torella, R. and D’Onofrio, F. (1987) Impaired glucose metabolism in heroin and methadone users. Hormone and Metabolic Research, 19, 430-433. doi:10.1055/s-2007-1011844
[33] Cunha-Oliveira, T., Rego, A.C., Garrido, J., Borges, F., Macedo, T. and Oliveira, C.R. (2007) Street heroin induces mitochondrial dysfunction and apoptosis in rat cortical neurons. Journal of Neurochemistry, 101, 543-554. doi:10.1111/j.1471-4159.2006.04406.x
[34] Hutchinson, M.R., Zhang, Y., Shridhar, M., Evans, J.H., Buchanan, M.M., Zhao, T.X., Slivka, P.F., Coats, B.D., Rezvani, N., Wieseler, J., et al. (2010) Evidence that opioids may have toll-like receptor 4 and MD-2 effects. Brain, Behavior, and Immunity, 24, 83-95. doi:10.1016/j.bbi.2009.08.004
[35] Adler, M.W., Geller, E.B., Chen, X. and Rogers, T.J. (2005) Viewing chemokines as a third major system of communication in the brain. AAPS Journals, 7, E865-E870. doi:10.1208/aapsj070484
[36] Anderson, J.E. (2000) A role for nitric oxide in muscle repair: Nitric oxide-mediated activation of muscle satellite cells. Molecular Biology of the Cell, 11, 1859-1874. doi:10.1091/mbc.11.5.1859
[37] Reece, A.S. (2011) Differing age related trajectories of dysfunction in several organ systems in opiate dependence. Aging Clinical and Experimental Research, 24, 85-96.
[38] Kim, T.W., Alford, D.P., Malabanan, A., Holick, M.F., Samet, J.H. (2006) Low bone density in patients receiving methadone maintenance treatment. Drug and Alcohol Dependence, 85, 258-262. doi:10.1016/j.drugalcdep.2006.05.027
[39] Reece, A.S. and Davidson, P. (2007) Deficit of circulating stem—Progenitor cells in opiate addiction: A pilot study. Substance Abuse Treatment, Prevention, and Policy, 2, 19-28. doi:10.1186/1747-597X-2-19

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