Tracking Early Atherosclerosis by Audiometry; A Review of Studies in a High Risk Population
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Jan 30, 2024
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Abstract
Objectives: Increasing levels of atherosclerosis correlate with increasing degrees of hearing loss. We hypothesized that arterial inflammation observed on FDG-PET/CT scans correlates with audiogram test results and that Major Adverse Cardiovascular Events occur in subjects with severe hearing loss (>40 dB).
Methods: A FDG-PET/CT imaging prospective study was performed in an NIH trial including 115 rheumatoid arthritis subjects over age 50 without a history of cardiovascular disease, and 22 subjects were selected for concurrent audiograms. All were evaluated by 18-fluorodeoxyglucose positron emission tomography computed tomography scans and audiogram tests, at baseline and 6 months. In our institution, 320 similar RA subjects were identified over age 50 with no prior cardiovascular disease and chart review completed for 10 years to evaluate MACE occurrence. Audiograms were available for the 320 retrospective patients.
Results: In the imaging study, at baseline there was a strong correlation between arterial inflammation on FDG-PET/CT and hearing test results (p<0.002). Hearing loss over 30 decibels was strongly associated with high levels of inflammation on FDG-PET/CT imaging. In the larger 320 retrospective group, there were 11 MACE (3.4%) in the 10 years period which occurred in subjects with even greater hearing loss (average measurement was over 50 dB).
Conclusion: Atherosclerosis was identified through FDG-PET/CT imaging studies and hearing tests. All MACE occurred in patients with significant hearing loss. Testing comprised a unique population with systemic inflammation from RA. If confirmed in larger studies in the general population, audiograms might provide a cost- effective substitute for FDG-PET/CT imaging and provide potentially an improved individual patient cardiovascular risk assessment. Audiograms may infer cardiovascular
Keywords:
Atherosclerosis, MACE, cardiovascular risk factor, FDG-PET/CT imaging, audiogram
Article Details
How to Cite
GREENWALD, Maria; BALL, JoAnn.
Tracking Early Atherosclerosis by Audiometry; A Review of Studies in a High Risk Population.
Medical Research Archives, [S.l.], v. 12, n. 1, jan. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4917>. Date accessed: 21 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i1.4917.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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3. Fischer M, Schubert C, Nondahl D, et.al. Subclinical atherosclerosis and increase risk of hearing impairment. Atherosclerosis 2015; 238(2):344-49.
4. Purves D, Augustine G, Fitzpatrick D, et.al. The Auditory Cortex. Neuroscience 2nd edition. Sunderland (MA): Sinauer Associates; 2001. Part of the National Library of Medicine bookshelf.
5. Greenwald K, Greenwald M, Ball J. Using audiometry to track atherosclerosis: Measuring a beneficial effect of methotrexate in rheumatoid arthritis. EMJ Rheumatol 2020;7:110-117.
6. Jafari Z, Kolb B, Mohajerani M. Age-related hearing loss and cognitive decline: MRI and cellular evidence. Annals of the New York Academy of Sciences 2021: 1500:17-33. dot:10.1111/nyas.14617.
7. Solomon D, Giles J, Liao K, Ridker P, Rist P, Glynn R, et.al. Reducing cardiovascular risk with immunomodulators: a randomized active comparator trial among patients with rheumatoid arthritis (the TARGET trial). Ann Rheum Dis 2022;0:1-7. dot:10.1136/ard-2022-223302.
8. Greenwald M, Gunberg S, Ball J, Garcia D. Hearing Loss As A Surrogate Marker For Early Atherosclerosis in A High-Risk Population: A Prospective Study. American Journal of Cardiology. 2023; ISSN 0002-9149, https://doi.org/10.1016/j.amjcard.2023.11.002.
9. Nibelung L, Christensen R, Danneskiold-Samsoe B, et.al. Validity and agreement between the 28-joint disease activity score based on C-reactive protein and erythrocyte sedimentation rate in patients with rheumatoid arthritis. Arthritis. 2015;2015:1-6.
10. Agency for Health Care Research and Quality. U.S. Preventive Services Task Force. 2011. Screening Adults Aged 50 Years or Older for Hearing Loss: A Review of the Evidence for the U.S. Preventive Services Task Force. Annals of Internal Medicine. 2011:154;347-355.
11. Tawakol A, Migrino R, Bashian G, et.al. In vivo 18-F-fluorodeoxygluscose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 2006;48:1818-24.
12. Rudd J, Myers K, Bansilal S, et.al. 18-Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol. 2007;50:892-6.
13. Font M, Fernandex A, Carvajal A, et.al. Imaging of early inflammation in low-to- moderate carotid stenosis by 18-FDG-PET. FBL. 2009; 14:3352-60.
14. Murthy VL. Clinical Quantification of Myocardial Blood Flow using Positron Emission Tomography: A Joint Position Paper of the Cardiovascular Council (CVC) of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) & the American Society of Nuclear Cardiology (ASNC). J Nucl Cardiol. 2017.
15. van Wijk D, Sjouke B, Figueroa A, et al. Nonpharmacological lipoprotein apheresis reduces arterial inflammation in Familial Hypercholesterolemia. J Am Coll Cardiol. 2014 Oct, 64 (14) 1418–1426. doi:10.1016/j.jacc.2014.01.088.
16. Holland-Carlsen P, Piri R, Madsen P, Revheim M, Werner T, Alavi A, et.al. Atherosclerosis burdens in diabetes mellitus: assessment by PET imaging. Int J Mol Sci. 2022, 23;10268. doi:10.3390/ijms231810268.
17. Moghbel M, AL-Zaghal A, Werner T, Constantinescu C, Hooiland-Carlsen P, Alavi A. The role of PET in evaluating atherosclerosis: a critical review. Semin Nuclear Med. 2018, 48;488-497. dot:10.1053/j.semnuclmed.2018.07.001
18. Jensen J, Binderup T, Grandjean C, Bentsen S, Ripa R, Kjaer A. Semaglutide reduces vascular inflammation investigated by PET. Atherosclerosis 2022;352:88-95.
19. Tawakol A, Fayad Z, Mogg R, et.al. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a FDG-PET/CT feasibility study. J Am Coll Cardiol. 2013;62:909-911.
20. Mizoguchi M, Tahara N, Tahara A, et.al. Pioglitazone attenuates atherosclerotic plaque inflammation: a randomized, comparator-controlled study using serial FDG-PET/CT imaging study of carotid artery and ascending aorta. JACC: Cardiovascular Imaging. 2011;4:1110-8.
21. Hansson G,. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2006;352:1685-95
22. Einabawi Y, Oikonomou E, Dey A, et.al. Association of biologic therapy with coronary inflammation in patients with psoriasis as assessed by perivascular fat attenuation index. JAMA Cardiol. 2019;4:855-891.
23. Barnabe C, Martine B, Ghali W. Systematic review and meta-analysis: anti-tumor necrosis factor alpha therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res. 2011;63:522-9.
24. Amigues I, Tugcu A, Russo C. et. al. Myocardial inflammation measured using 18-fluorodeoxyglucose Positron Emission Tomography with computed tomography is associated with disease activity in rheumatoid arthritis. Arthritis Rheum. 2019;71:496-506.
25. Nidorf S, Fiolet A, Mosterd A, et.al. Colchicine in patients with chronic coronary disease N Engl J Med. 2020;383:1838-1847.
26. Uchida Y, Nishita Y, Otsuka R, Sugiura S, Sone M, Yamasoba T, et.al. Aging brian and hearing:A mini-review. Frontiers in Aging Neuroscience. 2022;13:791604. doi:10.3389/fnagi.2021.791604.
27. Kim S, Lee C, Min C, You D, Choi H. Association between statin medication and hearing impairment in a national health screening cohort (n=17,548). Scientific Reports. 2021;11:14388. doi:10.1038/341598-21-93916-z.
28. Han H, Yes J, Park Y, Gwak H. Association between statin use and sensorineural hearing loss in type 2 diabetic patients. Pharmaceuticals. 2021;14:1076. doi:10.3390/ph14111076.
29. Manno F, Rodriguez-Cruces R, Kumar R, Ratnanather J, Lay C. Hearing loss impacts gray and white matter across the lifespan: systemic review, meta-analysis and meta-regression. Neuroimage. 2021; 231:117826. dot:10.1016/j.neuroimage:2021.117826
30. Ruan C, Mao X, Chen S, Wu S, Wang W. Subclinical atherosclerosis could increase the risk of hearing impairment in males: a community based cross-sectional survey of the Kailuan study. Frontiers in Neuroscience. 2022;16:813628. doi:10.3389/fnins.2022.813628.
31. Wattamwar K, Z Jason Qian, Jenna Otter, et.al. Increases in the rate of age-related hearing loss in the older old. JAMA Otolaryngology Head Neck. 2017;143:41-5.
32. Hult R, Kerschen S. Can improved cardiovascular health enhance auditory function. Hearing J. 2018:21;22-3.
33. Engdahl B, Aarhus L, Lie A, Tambs K. Cardiovascular risk factors and hearing loss: The HUNT study. Int J Audiol. 2015;54(12):958-66. doi: 10.3109/14992027.2015.1090631.
34. Nash SD, Cruickshanks KJ, Klein R, et al. The Prevalence of Hearing Impairment and Associated Risk Factors: The Beaver Dam Offspring Study. Arch Otolaryngol Head Neck Surg. 2011;137(5):432–439. doi:10.1001/archoto.2011.15.
35. Tan HE, Lan NSR, Knuiman MW, et.al. Associations between cardiovascular disease and its risk factors with hearing loss-A cross-sectional analysis. Clin Otolaryngol. 2018 Feb;43(1):172-181. doi: 10.1111/coa.12936.
36. Macias-Reyes H, Duran-Barragan S, Crdenas-Contreras C, Chavez-Martin C, et.al. Sensorineural hearing impairment and subclinical atherosclerosis in rheumatoid arthritis patients without traditional cardiovascular risk factors. Arch Rheumatology. 2016;31:208-214. doi:10.5606/ArchRheumatol.2016.5739.
37. Wissen S, Trip M, Smilde T, Graaf J, Stalenhoef A, Kastelein J. Differential hs-CRP reduction in patients with familial hypercholesterolemia treated with statin therapy. Atherosclerosis. 2002;165:361-366.
38. Iadecola C, Parish N. Framingham general cardiovascular risk score J Am Coll Cardiol. 2020;75:2535-2537.
39. Pooled Cohort Equation. Goff D, Lloyd-Jones D, Coady S, Bennett G, D’Agostino R, Gibbons R, et.al. Practice guidelines for 2013. J Am Coll Cardiol. 2014;63:2935-59.
40. European Systematic Coronary Risk Evaluation (SCORE) Conroy R, Pyorala K, Fitzgerald A, Sans S, Menotti A, De Backer G, et.al. SCORE project group: Estimation of ten-year of fatal cardiovascular disease in Europe. Eur Heart J. 2003;24:987-1003.
41. Arts E, Popa C, DenBroeder A,, et.al. Prediction of cardiovascular risk in rheumatoid arthritis: performance of original and adapted score algorithms. Ann Rheum Dis. 2016;75:624-80.
42. Crown C, Rollefstad S, Idaho E, et.sal. Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2018;77:48-54.
43. Chia E, Wang J, Rochtchina E, Cumming R, Newall R, Mitchell P. Hearing impairment and health-related quality of life: the Blue Mountains Hearing Study. Ear Hear. 2007;28:187-195.
44. Agrawal Y, Platz E, Niparko J. Prevalence of hearing loss and differences by demographic characteristics among US adults: data from the National Health and Nutrition Examination Survey (NHANES)1999-2004. Arch Intern Med. 2008;168:1522-1530.
45. Moscicki E, Elkins E, Baum H, McNamara P. Hearing loss in the elderly: an epidemiological study of the Framingham Heart Study Cohort. Ear Hear. 1985;6:184-190.
46. Cruickshanks K, Wiley T, Tweed T, et.al. Prevalence of hearing loss in older adults in Beaver Dam Wisconsin: the epidemiology of hearing loss study. Am J Epidemiol. 1998;148:879-886.
47. Ytterberg S, Bhatt D, Mikuls T, et.al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. New Engl J Med. 2022;386:316-326.
48. Charles-Schoeman D, Choy E, MacInnes I, Mysler E, Nash P, Yamaoka K, et.al. MACE and VTE across Upadacitinib clinical trial programs in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. RMD Open. 2023;9:e003392. doi: 10.1136/rmdopen-2023-003392.
49. European Medicines Agency/Committee for Medicinal Products for Human Use. Published October 30, 2023. Accessed November 16, 2023. “Baricitinib should only be used if no suitable treatment alternatives are available in patients aged 65 years or above, in patients with a history of cardiovascular disease (such as heart attack or stroke) or with risk factors such as current or previous long-term smokers, or in patients at increased risk of cancer.” Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/olumianti
50. Choi H, Herhan H, Seeger J, Robins J, Wolfe F. Methotrexate and morality in patients with rheumatoid arthritis: a prospective study. Lancet. 2002;359:1173-1177.
51. Wasko M et.al. Propensity adjusted association of methotrexate with overall survival in rheumatoid arthritis. Arthritis & Rheumatism. 2013;65:334-342.
52. Figueroa A, Adodelbaky A, Troung Q, et.al. Measurement of arterial activity on routine FDG-PET/CT images improves prediction of risk of future cardiovascular events. JACC Cardiovascular Imaging. 2013;6:1250-9.
53. Iwatsuka, R, Matsui Y, Yonetsu T, O’Uchi T, Matsumura A, HashimotoY, et.al. Arterial inflammation measured by 18FDG-PET/CT to predict coronary events in older subjects Atherosclerosis. 2018; 268;:49-54. dot:10.1016/atherosclerosis.2017.11.016.
54. Master@Heart DeBosscher R, Dousing C, Claus P, Bogaert J, Dymarkowski S, Goetschalckx K, et.al. Lifelong endurance exercise and its relation with coronary atherosclerosis European Heart J. March 2023:1-12. doi:10.1093/eurheartj/ehad152.
55. Hofman A, Brussels G, Darwish Met.al. The Rotterdam Study: 2016 objectives and design update Eur J Epidemiol. 2015;30:661-708. dot:10.1007/s10654-015-0082-x.
56. Bild D, Bluemke D, Burde G, et.al. Mutli-ethnic study of atherosclerosis: objectives and design. Am J Epidemiol. 2002;156:871-881. doi:10.1093/aje/kwf113.
57. Friedland D, Cederberg C, Tarima S. Audiometric pattern as a predictor of cardiovascular status: development of a model. Laryngoscope. 2009;119:473-86. doi:10.1002/Iary.20130.
2. Gates G, Cobb J, D’Agostino R, Wolf P. The relation of hearing in the elderly to the presence of cardiovascular disease and cardiovascular risk factors. Arch Otolaryngol Head Neck Surg 1993;119:156-61.
3. Fischer M, Schubert C, Nondahl D, et.al. Subclinical atherosclerosis and increase risk of hearing impairment. Atherosclerosis 2015; 238(2):344-49.
4. Purves D, Augustine G, Fitzpatrick D, et.al. The Auditory Cortex. Neuroscience 2nd edition. Sunderland (MA): Sinauer Associates; 2001. Part of the National Library of Medicine bookshelf.
5. Greenwald K, Greenwald M, Ball J. Using audiometry to track atherosclerosis: Measuring a beneficial effect of methotrexate in rheumatoid arthritis. EMJ Rheumatol 2020;7:110-117.
6. Jafari Z, Kolb B, Mohajerani M. Age-related hearing loss and cognitive decline: MRI and cellular evidence. Annals of the New York Academy of Sciences 2021: 1500:17-33. dot:10.1111/nyas.14617.
7. Solomon D, Giles J, Liao K, Ridker P, Rist P, Glynn R, et.al. Reducing cardiovascular risk with immunomodulators: a randomized active comparator trial among patients with rheumatoid arthritis (the TARGET trial). Ann Rheum Dis 2022;0:1-7. dot:10.1136/ard-2022-223302.
8. Greenwald M, Gunberg S, Ball J, Garcia D. Hearing Loss As A Surrogate Marker For Early Atherosclerosis in A High-Risk Population: A Prospective Study. American Journal of Cardiology. 2023; ISSN 0002-9149, https://doi.org/10.1016/j.amjcard.2023.11.002.
9. Nibelung L, Christensen R, Danneskiold-Samsoe B, et.al. Validity and agreement between the 28-joint disease activity score based on C-reactive protein and erythrocyte sedimentation rate in patients with rheumatoid arthritis. Arthritis. 2015;2015:1-6.
10. Agency for Health Care Research and Quality. U.S. Preventive Services Task Force. 2011. Screening Adults Aged 50 Years or Older for Hearing Loss: A Review of the Evidence for the U.S. Preventive Services Task Force. Annals of Internal Medicine. 2011:154;347-355.
11. Tawakol A, Migrino R, Bashian G, et.al. In vivo 18-F-fluorodeoxygluscose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 2006;48:1818-24.
12. Rudd J, Myers K, Bansilal S, et.al. 18-Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol. 2007;50:892-6.
13. Font M, Fernandex A, Carvajal A, et.al. Imaging of early inflammation in low-to- moderate carotid stenosis by 18-FDG-PET. FBL. 2009; 14:3352-60.
14. Murthy VL. Clinical Quantification of Myocardial Blood Flow using Positron Emission Tomography: A Joint Position Paper of the Cardiovascular Council (CVC) of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) & the American Society of Nuclear Cardiology (ASNC). J Nucl Cardiol. 2017.
15. van Wijk D, Sjouke B, Figueroa A, et al. Nonpharmacological lipoprotein apheresis reduces arterial inflammation in Familial Hypercholesterolemia. J Am Coll Cardiol. 2014 Oct, 64 (14) 1418–1426. doi:10.1016/j.jacc.2014.01.088.
16. Holland-Carlsen P, Piri R, Madsen P, Revheim M, Werner T, Alavi A, et.al. Atherosclerosis burdens in diabetes mellitus: assessment by PET imaging. Int J Mol Sci. 2022, 23;10268. doi:10.3390/ijms231810268.
17. Moghbel M, AL-Zaghal A, Werner T, Constantinescu C, Hooiland-Carlsen P, Alavi A. The role of PET in evaluating atherosclerosis: a critical review. Semin Nuclear Med. 2018, 48;488-497. dot:10.1053/j.semnuclmed.2018.07.001
18. Jensen J, Binderup T, Grandjean C, Bentsen S, Ripa R, Kjaer A. Semaglutide reduces vascular inflammation investigated by PET. Atherosclerosis 2022;352:88-95.
19. Tawakol A, Fayad Z, Mogg R, et.al. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a FDG-PET/CT feasibility study. J Am Coll Cardiol. 2013;62:909-911.
20. Mizoguchi M, Tahara N, Tahara A, et.al. Pioglitazone attenuates atherosclerotic plaque inflammation: a randomized, comparator-controlled study using serial FDG-PET/CT imaging study of carotid artery and ascending aorta. JACC: Cardiovascular Imaging. 2011;4:1110-8.
21. Hansson G,. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2006;352:1685-95
22. Einabawi Y, Oikonomou E, Dey A, et.al. Association of biologic therapy with coronary inflammation in patients with psoriasis as assessed by perivascular fat attenuation index. JAMA Cardiol. 2019;4:855-891.
23. Barnabe C, Martine B, Ghali W. Systematic review and meta-analysis: anti-tumor necrosis factor alpha therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res. 2011;63:522-9.
24. Amigues I, Tugcu A, Russo C. et. al. Myocardial inflammation measured using 18-fluorodeoxyglucose Positron Emission Tomography with computed tomography is associated with disease activity in rheumatoid arthritis. Arthritis Rheum. 2019;71:496-506.
25. Nidorf S, Fiolet A, Mosterd A, et.al. Colchicine in patients with chronic coronary disease N Engl J Med. 2020;383:1838-1847.
26. Uchida Y, Nishita Y, Otsuka R, Sugiura S, Sone M, Yamasoba T, et.al. Aging brian and hearing:A mini-review. Frontiers in Aging Neuroscience. 2022;13:791604. doi:10.3389/fnagi.2021.791604.
27. Kim S, Lee C, Min C, You D, Choi H. Association between statin medication and hearing impairment in a national health screening cohort (n=17,548). Scientific Reports. 2021;11:14388. doi:10.1038/341598-21-93916-z.
28. Han H, Yes J, Park Y, Gwak H. Association between statin use and sensorineural hearing loss in type 2 diabetic patients. Pharmaceuticals. 2021;14:1076. doi:10.3390/ph14111076.
29. Manno F, Rodriguez-Cruces R, Kumar R, Ratnanather J, Lay C. Hearing loss impacts gray and white matter across the lifespan: systemic review, meta-analysis and meta-regression. Neuroimage. 2021; 231:117826. dot:10.1016/j.neuroimage:2021.117826
30. Ruan C, Mao X, Chen S, Wu S, Wang W. Subclinical atherosclerosis could increase the risk of hearing impairment in males: a community based cross-sectional survey of the Kailuan study. Frontiers in Neuroscience. 2022;16:813628. doi:10.3389/fnins.2022.813628.
31. Wattamwar K, Z Jason Qian, Jenna Otter, et.al. Increases in the rate of age-related hearing loss in the older old. JAMA Otolaryngology Head Neck. 2017;143:41-5.
32. Hult R, Kerschen S. Can improved cardiovascular health enhance auditory function. Hearing J. 2018:21;22-3.
33. Engdahl B, Aarhus L, Lie A, Tambs K. Cardiovascular risk factors and hearing loss: The HUNT study. Int J Audiol. 2015;54(12):958-66. doi: 10.3109/14992027.2015.1090631.
34. Nash SD, Cruickshanks KJ, Klein R, et al. The Prevalence of Hearing Impairment and Associated Risk Factors: The Beaver Dam Offspring Study. Arch Otolaryngol Head Neck Surg. 2011;137(5):432–439. doi:10.1001/archoto.2011.15.
35. Tan HE, Lan NSR, Knuiman MW, et.al. Associations between cardiovascular disease and its risk factors with hearing loss-A cross-sectional analysis. Clin Otolaryngol. 2018 Feb;43(1):172-181. doi: 10.1111/coa.12936.
36. Macias-Reyes H, Duran-Barragan S, Crdenas-Contreras C, Chavez-Martin C, et.al. Sensorineural hearing impairment and subclinical atherosclerosis in rheumatoid arthritis patients without traditional cardiovascular risk factors. Arch Rheumatology. 2016;31:208-214. doi:10.5606/ArchRheumatol.2016.5739.
37. Wissen S, Trip M, Smilde T, Graaf J, Stalenhoef A, Kastelein J. Differential hs-CRP reduction in patients with familial hypercholesterolemia treated with statin therapy. Atherosclerosis. 2002;165:361-366.
38. Iadecola C, Parish N. Framingham general cardiovascular risk score J Am Coll Cardiol. 2020;75:2535-2537.
39. Pooled Cohort Equation. Goff D, Lloyd-Jones D, Coady S, Bennett G, D’Agostino R, Gibbons R, et.al. Practice guidelines for 2013. J Am Coll Cardiol. 2014;63:2935-59.
40. European Systematic Coronary Risk Evaluation (SCORE) Conroy R, Pyorala K, Fitzgerald A, Sans S, Menotti A, De Backer G, et.al. SCORE project group: Estimation of ten-year of fatal cardiovascular disease in Europe. Eur Heart J. 2003;24:987-1003.
41. Arts E, Popa C, DenBroeder A,, et.al. Prediction of cardiovascular risk in rheumatoid arthritis: performance of original and adapted score algorithms. Ann Rheum Dis. 2016;75:624-80.
42. Crown C, Rollefstad S, Idaho E, et.sal. Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2018;77:48-54.
43. Chia E, Wang J, Rochtchina E, Cumming R, Newall R, Mitchell P. Hearing impairment and health-related quality of life: the Blue Mountains Hearing Study. Ear Hear. 2007;28:187-195.
44. Agrawal Y, Platz E, Niparko J. Prevalence of hearing loss and differences by demographic characteristics among US adults: data from the National Health and Nutrition Examination Survey (NHANES)1999-2004. Arch Intern Med. 2008;168:1522-1530.
45. Moscicki E, Elkins E, Baum H, McNamara P. Hearing loss in the elderly: an epidemiological study of the Framingham Heart Study Cohort. Ear Hear. 1985;6:184-190.
46. Cruickshanks K, Wiley T, Tweed T, et.al. Prevalence of hearing loss in older adults in Beaver Dam Wisconsin: the epidemiology of hearing loss study. Am J Epidemiol. 1998;148:879-886.
47. Ytterberg S, Bhatt D, Mikuls T, et.al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. New Engl J Med. 2022;386:316-326.
48. Charles-Schoeman D, Choy E, MacInnes I, Mysler E, Nash P, Yamaoka K, et.al. MACE and VTE across Upadacitinib clinical trial programs in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. RMD Open. 2023;9:e003392. doi: 10.1136/rmdopen-2023-003392.
49. European Medicines Agency/Committee for Medicinal Products for Human Use. Published October 30, 2023. Accessed November 16, 2023. “Baricitinib should only be used if no suitable treatment alternatives are available in patients aged 65 years or above, in patients with a history of cardiovascular disease (such as heart attack or stroke) or with risk factors such as current or previous long-term smokers, or in patients at increased risk of cancer.” Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/olumianti
50. Choi H, Herhan H, Seeger J, Robins J, Wolfe F. Methotrexate and morality in patients with rheumatoid arthritis: a prospective study. Lancet. 2002;359:1173-1177.
51. Wasko M et.al. Propensity adjusted association of methotrexate with overall survival in rheumatoid arthritis. Arthritis & Rheumatism. 2013;65:334-342.
52. Figueroa A, Adodelbaky A, Troung Q, et.al. Measurement of arterial activity on routine FDG-PET/CT images improves prediction of risk of future cardiovascular events. JACC Cardiovascular Imaging. 2013;6:1250-9.
53. Iwatsuka, R, Matsui Y, Yonetsu T, O’Uchi T, Matsumura A, HashimotoY, et.al. Arterial inflammation measured by 18FDG-PET/CT to predict coronary events in older subjects Atherosclerosis. 2018; 268;:49-54. dot:10.1016/atherosclerosis.2017.11.016.
54. Master@Heart DeBosscher R, Dousing C, Claus P, Bogaert J, Dymarkowski S, Goetschalckx K, et.al. Lifelong endurance exercise and its relation with coronary atherosclerosis European Heart J. March 2023:1-12. doi:10.1093/eurheartj/ehad152.
55. Hofman A, Brussels G, Darwish Met.al. The Rotterdam Study: 2016 objectives and design update Eur J Epidemiol. 2015;30:661-708. dot:10.1007/s10654-015-0082-x.
56. Bild D, Bluemke D, Burde G, et.al. Mutli-ethnic study of atherosclerosis: objectives and design. Am J Epidemiol. 2002;156:871-881. doi:10.1093/aje/kwf113.
57. Friedland D, Cederberg C, Tarima S. Audiometric pattern as a predictor of cardiovascular status: development of a model. Laryngoscope. 2009;119:473-86. doi:10.1002/Iary.20130.