The Influence of Abdominal Obesity on the Accuracy of Cardiovascular Risk Prediction in Rheumatoid Arthritis
Main Article Content
Abstract
Objectives. Underweight patients with rheumatoid arthritis incur greater total and cardiovascular mortality compared to overweight or obese. We explored whether obesity confounded cardiovascular risk estimates and the potential utility of noninvasive coronary atherosclerosis assessment and cardiac damage biomarkers in optimizing risk prediction in obese patients with rheumatoid arthritis.
Methods. We evaluated 150 participants undergoing screening atherosclerosis evaluation with coronary computed tomography angiography and follow-up over 6.0±2.4 years. Framingham 2008 modified general cardiovascular risk score was computed at baseline. Obesity was defined as waist circumference >88 cm in females and >102 cm in males. Serum highly-sensitive cardiac troponin I (hs-cTnI) and leptin were measured at baseline.
Results. An interaction between the Framingham risk score and obesity on cardiovascular risk was observed (p=0.032); lower estimates were seen in obese (area under the curve-AUC 0.660, 95% CI 0.487-0.832) vs. non-obese patients (AUC 0.952, 95% CI 0.897-1.007, p=0.002). Likewise, risk estimates were inferior in patients with high (>22.1 ng/ml) vs. low leptin (AUC 0.618, 95% CI 0.393-0.842 vs. 0.874, 95% CI 0.772-0.976, p=0.042). In obese patients, sequential addition of the top highly-sensitive cardiac troponin I tertile values and extensive atherosclerotic plaque (>5 segments) information to a base model including the Framingham risk score alone significantly improved risk estimates, based on changes in net reclassification index (1.093 95% CI 0.517-1.574), integrated discrimination improvement (0.188, 95% CI 0.060-0.526), and AUC (0.179, 95% CI 0.058-0.378, p=0.02). The final, combined model accurately predicted 83.9% of incident cardiovascular events.
Conclusion. Obesity attenuated cardiovascular risk estimate accuracy in patients with rheumatoid arthritis. Risk optimization employing non-invasive assessment of coronary atherosclerosis burden and serum cardiac damage biomarkers may warrant further study.
Keywords:
Rheumatoid arthritis, cardiovascular disease, obesity, computed tomography, highly-sensitive cardiac troponin-I, leptin
Article Details
How to Cite
KARPOUZAS, George A et al.
The Influence of Abdominal Obesity on the Accuracy of Cardiovascular Risk Prediction in Rheumatoid Arthritis.
Medical Research Archives, [S.l.], v. 11, n. 9, sep. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4432>. Date accessed: 03 may 2024.
doi: https://doi.org/10.18103/mra.v11i9.4432.
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. Carbone S, Canada JM, Billingsley HE, Siddiqui MS, Elagizi A, Lavie CJ. Obesity paradox in cardiovascular disease: where do we stand? Vasc Health Risk Manag. 2019;15:89-100.
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7. Ljung L, Rantapää-Dahlqvist S. Abdominal obesity, gender and the risk of rheumatoid arthritis - a nested case-control study. Arthritis Res Ther. 2016;18(1):277.
8. Tang B, Shi H, Alfredsson L, Klareskog L, Padyukov L, Jiang X. Obesity-related traits and the development of rheumatoid arthritis: evidence from genetic data. Arthritis Rheumatol. 2021;73(2):203-211.
9. Escalante A, Haas RW, del Rincón I. Paradoxical effect of body mass index on survival in rheumatoid arthritis: role of comorbidity and systemic inflammation. Arch Intern Med. 2005;165(14):1624-1629.
10. Kremers HM, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Prognostic importance of low body mass index in relation to cardiovascular mortality in rheumatoid arthritis. Arthritis Rheum. 2004;50(11):3450-3457.
11. Després JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126(10):1301-1313.
12. Huxley R, Mendis S, Zheleznyakov E, Reddy S, Chan J. Body mass index, waist circumference and waist:hip ratio as predictors of cardiovascular risk--a review of the literature. Eur J Clin Nutr. 2010;64(1):16-22.
13. Swainson MG, Batterham AM, Tsakirides C, Rutherford ZH, Hind K. Prediction of whole-body fat percentage and visceral adipose tissue mass from five anthropometric variables. PLoS One. 2017;12(5):e0177175.
14. Roriz AKC, Passos LCS, de Oliveira CC, Eickemberg M, Moreira P de A, Sampaio LR. Evaluation of the accuracy of anthropometric clinical indicators of visceral fat in adults and elderly. PLoS One. 2014;9(7):e103499.
15. Giles JT, Allison M, Blumenthal RS, et al. Abdominal adiposity in rheumatoid arthritis: association with cardiometabolic risk factors and disease characteristics. Arthritis Rheum. 2010;62(11):3173-3182.
16. Trevaskis JL, Coffey T, Cole R, et al. Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: magnitude and mechanisms. Endocrinology. 2008;149(11): 5679-5687.
17. Banks WA. Role of the blood-brain barrier in the evolution of feeding and cognition. Ann N Y Acad Sci. 2012;1264(1):13-19.
18. Khaki-Khatibi F, Shademan B, Gholikhani-Darbroud R, Nourazarian A, Radagdam S, Porzour M. Gene polymorphism of leptin and risk for heart disease, obesity, and high BMI: a systematic review and pooled analysis in adult obese subjects. Horm Mol Biol Clin Investig. 2023;44(1):11-20.
19. Crowson CS, Gabriel SE, Semb AG, et al. Rheumatoid arthritis-specific cardiovascular risk scores are not superior to general risk scores: a validation analysis of patients from seven countries. Rheumatology (Oxford). 2017;56 (7):1102-1110.
20. Colaco K, Ocampo V, Ayala AP, et al. Predictive utility of cardiovascular risk prediction algorithms in inflammatory rheumatic diseases: a systematic review. J Rheumatol. 2020;47(6):928-938.
21. Karpouzas GA, Malpeso J, Choi TY, Li D, Munoz S, Budoff MJ. Prevalence, extent and composition of coronary plaque in patients with rheumatoid arthritis without symptoms or prior diagnosis of coronary artery disease. Ann Rheum Dis. 2014;73(10):1797-1804.
22. Karpouzas GA, Estis J, Todd J, Budoff MJ. Occult coronary plaque presence and burden predict cardiovascular events in patients with rheumatoid arthritis. Arthritis Rheumatol. 2017;69 (suppl 10).
23. Karpouzas GA, Estis J, Rezaeian P, Todd J, Budoff MJ. High-sensitivity cardiac troponin I is a biomarker for occult coronary plaque burden and cardiovascular events in patients with rheumatoid arthritis. Rheumatology (Oxford). 2018;57(6):1080-1088.
24. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Biologics may prevent cardiovascular events in rheumatoid arthritis by Inhibiting coronary plaque formation and stabilizing high-risk lesions. Arthritis Rheumatol. 2020;72:1467-1475.
25. SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet. 2015;385(9985):2383-2391.
26. SCOT-HEART Investigators, Newby DE, Adamson PD, et al. Coronary CT angiography and 5-year risk of myocardial infarction. N Engl J Med. 2018;379(10):924-933.
27. Douglas PS, Hoffmann U, Lee KL, et al. PROspective Multicenter Imaging Study for Evaluation of chest pain: rationale and design of the PROMISE trial. Am Heart J. 2014;167(6):796-803.e1.
28. Golüke NMS, Schoffelmeer MA, De Jonghe A, Emmelot-Vonk MH, De Jong PA, Koek HL. Serum biomarkers for arterial calcification in humans: a systematic review. Bone Rep. 2022;17:101599.
29. Romero-Cabrera JL, Ankeny J, Fernández-Montero A, Kales SN, Smith DL. A systematic review and meta-analysis of advanced biomarkers for predicting incident cardiovascular disease among asymptomatic middle-aged adults. Int J Mol Sci. 2022;23(21):13540.
30. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008;52(21):1724-1732.
31. Leipsic J, Abbara S, Achenbach S, et al. SCCT guidelines for the interpretation and reporting of coronary CT angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee. J Cardiovasc Comput Tomogr. 2014;8(5):342-358.
32. Pagali SR, Madaj P, Gupta M, et al. Interobserver variations of plaque severity score and segment stenosis score in coronary arteries using 64 slice multidetector computed tomography: a substudy of the ACCURACY trial. J Cardiovasc Comput Tomogr. 2010;4(5):312-318.
33. Bittencourt MS, Hulten E, Ghoshhajra B, et al. Prognostic value of nonobstructive and obstructive coronary artery disease detected by coronary computed tomography angiography to identify cardiovascular events. Circ Cardiovasc Imaging. 2014;7(2):282-291.
34. D’Agostino RB, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743-753.
35. Karpouzas GA, Papotti B, Ormseth SR, et al. Serum cholesterol loading capacity on macrophages is regulated by seropositivity and C-reactive protein in rheumatoid arthritis patients. Rheumatology (Oxford). 2023;62(3):1254-1263.
36. Alexopoulos N, Katritsis D, Raggi P. Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis. Atherosclerosis. 2014;233(1):104-112.
37. Heo M, Kabat GC, Gallagher D, Heymsfield SB, Rohan TE. Optimal scaling of weight and waist circumference to height for maximal association with DXA-measured total body fat mass by sex, age and race/ethnicity. Int J Obes (Lond). 2013;37(8):1154-1160.
38. Koster A, Murphy RA, Eiriksdottir G, et al. Fat distribution and mortality: the AGES-Reykjavik Study. Obesity (Silver Spring). 2015;23(4): 893-897.
39. Mahabadi AA, Massaro JM, Rosito GA, et al. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J. 2009;30(7):850-856.
40. Marques MD, Santos RD, Parga JR, et al. Relation between visceral fat and coronary artery disease evaluated by multidetector computed tomography. Atherosclerosis. 2010; 209(2):481-486.
41. Lear SA, Humphries KH, Kohli S, Frohlich JJ, Birmingham CL, Mancini GBJ. Visceral adipose tissue, a potential risk factor for carotid atherosclerosis: results of the Multicultural Community Health Assessment Trial (M-CHAT). Stroke. 2007;38(9):2422-2429.
42. Yoshida T, Hashimoto M, Kawahara R, et al. Non-obese visceral adiposity is associated with the risk of atherosclerosis in Japanese patients with rheumatoid arthritis: a cross-sectional study. Rheumatol Int. 2018;38(9):1679-1689.
43. Karpouzas GA, Rezaeian P, Ormseth SR, Hollan I, Budoff MJ. Epicardial adipose tissue volume as a marker of subclinical coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheumatol. 2021;73(8):1412-1420.
44. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. The impact of statins on coronary atherosclerosis progression and long-term cardiovascular disease risk in rheumatoid arthritis. Rheumatology (Oxford). 2022;61(5):1857-1866.
45. Borges MD, Franca EL, Fujimori M, et al. Relationship between proinflammatory cytokines/chemokines and adipokines in serum of young adults with obesity. Endocr Metab Immune Disord Drug Targets. 2018;18(3):260-267.
46. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Impact of cumulative inflammation, cardiac risk factors, and medication exposure on coronary atherosclerosis progression in rheumatoid arthritis. Arthritis Rheumatol. 2020;72(3):400-408.
2. Agca R, Heslinga SC, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017;76(1):17-28.
3. Carbone S, Canada JM, Billingsley HE, Siddiqui MS, Elagizi A, Lavie CJ. Obesity paradox in cardiovascular disease: where do we stand? Vasc Health Risk Manag. 2019;15:89-100.
4. Battineni G, Sagaro GG, Chintalapudi N, Amenta F, Tomassoni D, Tayebati SK. Impact of obesity-induced inflammation on cardiovascular diseases (CVD). Int J Mol Sci. 2021;22(9):4798.
5. Albrecht K, Richter A, Callhoff J, et al. Body mass index distribution in rheumatoid arthritis: a collaborative analysis from three large German rheumatoid arthritis databases. Arthritis Res Ther. 2016;18:149.
6. Bhole VM, Choi HK, Burns LC, et al. Differences in body mass index among individuals with PsA, psoriasis, RA and the general population. Rheumatology (Oxford). 2012;51(3):552-556.
7. Ljung L, Rantapää-Dahlqvist S. Abdominal obesity, gender and the risk of rheumatoid arthritis - a nested case-control study. Arthritis Res Ther. 2016;18(1):277.
8. Tang B, Shi H, Alfredsson L, Klareskog L, Padyukov L, Jiang X. Obesity-related traits and the development of rheumatoid arthritis: evidence from genetic data. Arthritis Rheumatol. 2021;73(2):203-211.
9. Escalante A, Haas RW, del Rincón I. Paradoxical effect of body mass index on survival in rheumatoid arthritis: role of comorbidity and systemic inflammation. Arch Intern Med. 2005;165(14):1624-1629.
10. Kremers HM, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Prognostic importance of low body mass index in relation to cardiovascular mortality in rheumatoid arthritis. Arthritis Rheum. 2004;50(11):3450-3457.
11. Després JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126(10):1301-1313.
12. Huxley R, Mendis S, Zheleznyakov E, Reddy S, Chan J. Body mass index, waist circumference and waist:hip ratio as predictors of cardiovascular risk--a review of the literature. Eur J Clin Nutr. 2010;64(1):16-22.
13. Swainson MG, Batterham AM, Tsakirides C, Rutherford ZH, Hind K. Prediction of whole-body fat percentage and visceral adipose tissue mass from five anthropometric variables. PLoS One. 2017;12(5):e0177175.
14. Roriz AKC, Passos LCS, de Oliveira CC, Eickemberg M, Moreira P de A, Sampaio LR. Evaluation of the accuracy of anthropometric clinical indicators of visceral fat in adults and elderly. PLoS One. 2014;9(7):e103499.
15. Giles JT, Allison M, Blumenthal RS, et al. Abdominal adiposity in rheumatoid arthritis: association with cardiometabolic risk factors and disease characteristics. Arthritis Rheum. 2010;62(11):3173-3182.
16. Trevaskis JL, Coffey T, Cole R, et al. Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: magnitude and mechanisms. Endocrinology. 2008;149(11): 5679-5687.
17. Banks WA. Role of the blood-brain barrier in the evolution of feeding and cognition. Ann N Y Acad Sci. 2012;1264(1):13-19.
18. Khaki-Khatibi F, Shademan B, Gholikhani-Darbroud R, Nourazarian A, Radagdam S, Porzour M. Gene polymorphism of leptin and risk for heart disease, obesity, and high BMI: a systematic review and pooled analysis in adult obese subjects. Horm Mol Biol Clin Investig. 2023;44(1):11-20.
19. Crowson CS, Gabriel SE, Semb AG, et al. Rheumatoid arthritis-specific cardiovascular risk scores are not superior to general risk scores: a validation analysis of patients from seven countries. Rheumatology (Oxford). 2017;56 (7):1102-1110.
20. Colaco K, Ocampo V, Ayala AP, et al. Predictive utility of cardiovascular risk prediction algorithms in inflammatory rheumatic diseases: a systematic review. J Rheumatol. 2020;47(6):928-938.
21. Karpouzas GA, Malpeso J, Choi TY, Li D, Munoz S, Budoff MJ. Prevalence, extent and composition of coronary plaque in patients with rheumatoid arthritis without symptoms or prior diagnosis of coronary artery disease. Ann Rheum Dis. 2014;73(10):1797-1804.
22. Karpouzas GA, Estis J, Todd J, Budoff MJ. Occult coronary plaque presence and burden predict cardiovascular events in patients with rheumatoid arthritis. Arthritis Rheumatol. 2017;69 (suppl 10).
23. Karpouzas GA, Estis J, Rezaeian P, Todd J, Budoff MJ. High-sensitivity cardiac troponin I is a biomarker for occult coronary plaque burden and cardiovascular events in patients with rheumatoid arthritis. Rheumatology (Oxford). 2018;57(6):1080-1088.
24. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Biologics may prevent cardiovascular events in rheumatoid arthritis by Inhibiting coronary plaque formation and stabilizing high-risk lesions. Arthritis Rheumatol. 2020;72:1467-1475.
25. SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet. 2015;385(9985):2383-2391.
26. SCOT-HEART Investigators, Newby DE, Adamson PD, et al. Coronary CT angiography and 5-year risk of myocardial infarction. N Engl J Med. 2018;379(10):924-933.
27. Douglas PS, Hoffmann U, Lee KL, et al. PROspective Multicenter Imaging Study for Evaluation of chest pain: rationale and design of the PROMISE trial. Am Heart J. 2014;167(6):796-803.e1.
28. Golüke NMS, Schoffelmeer MA, De Jonghe A, Emmelot-Vonk MH, De Jong PA, Koek HL. Serum biomarkers for arterial calcification in humans: a systematic review. Bone Rep. 2022;17:101599.
29. Romero-Cabrera JL, Ankeny J, Fernández-Montero A, Kales SN, Smith DL. A systematic review and meta-analysis of advanced biomarkers for predicting incident cardiovascular disease among asymptomatic middle-aged adults. Int J Mol Sci. 2022;23(21):13540.
30. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008;52(21):1724-1732.
31. Leipsic J, Abbara S, Achenbach S, et al. SCCT guidelines for the interpretation and reporting of coronary CT angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee. J Cardiovasc Comput Tomogr. 2014;8(5):342-358.
32. Pagali SR, Madaj P, Gupta M, et al. Interobserver variations of plaque severity score and segment stenosis score in coronary arteries using 64 slice multidetector computed tomography: a substudy of the ACCURACY trial. J Cardiovasc Comput Tomogr. 2010;4(5):312-318.
33. Bittencourt MS, Hulten E, Ghoshhajra B, et al. Prognostic value of nonobstructive and obstructive coronary artery disease detected by coronary computed tomography angiography to identify cardiovascular events. Circ Cardiovasc Imaging. 2014;7(2):282-291.
34. D’Agostino RB, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743-753.
35. Karpouzas GA, Papotti B, Ormseth SR, et al. Serum cholesterol loading capacity on macrophages is regulated by seropositivity and C-reactive protein in rheumatoid arthritis patients. Rheumatology (Oxford). 2023;62(3):1254-1263.
36. Alexopoulos N, Katritsis D, Raggi P. Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis. Atherosclerosis. 2014;233(1):104-112.
37. Heo M, Kabat GC, Gallagher D, Heymsfield SB, Rohan TE. Optimal scaling of weight and waist circumference to height for maximal association with DXA-measured total body fat mass by sex, age and race/ethnicity. Int J Obes (Lond). 2013;37(8):1154-1160.
38. Koster A, Murphy RA, Eiriksdottir G, et al. Fat distribution and mortality: the AGES-Reykjavik Study. Obesity (Silver Spring). 2015;23(4): 893-897.
39. Mahabadi AA, Massaro JM, Rosito GA, et al. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J. 2009;30(7):850-856.
40. Marques MD, Santos RD, Parga JR, et al. Relation between visceral fat and coronary artery disease evaluated by multidetector computed tomography. Atherosclerosis. 2010; 209(2):481-486.
41. Lear SA, Humphries KH, Kohli S, Frohlich JJ, Birmingham CL, Mancini GBJ. Visceral adipose tissue, a potential risk factor for carotid atherosclerosis: results of the Multicultural Community Health Assessment Trial (M-CHAT). Stroke. 2007;38(9):2422-2429.
42. Yoshida T, Hashimoto M, Kawahara R, et al. Non-obese visceral adiposity is associated with the risk of atherosclerosis in Japanese patients with rheumatoid arthritis: a cross-sectional study. Rheumatol Int. 2018;38(9):1679-1689.
43. Karpouzas GA, Rezaeian P, Ormseth SR, Hollan I, Budoff MJ. Epicardial adipose tissue volume as a marker of subclinical coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheumatol. 2021;73(8):1412-1420.
44. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. The impact of statins on coronary atherosclerosis progression and long-term cardiovascular disease risk in rheumatoid arthritis. Rheumatology (Oxford). 2022;61(5):1857-1866.
45. Borges MD, Franca EL, Fujimori M, et al. Relationship between proinflammatory cytokines/chemokines and adipokines in serum of young adults with obesity. Endocr Metab Immune Disord Drug Targets. 2018;18(3):260-267.
46. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Impact of cumulative inflammation, cardiac risk factors, and medication exposure on coronary atherosclerosis progression in rheumatoid arthritis. Arthritis Rheumatol. 2020;72(3):400-408.