Hand and heart, hand in hand: is radiological hand osteoarthritis associated with atherosclerosis?

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1 International Journal of Rheumatic Diseases 2014; 17: ORIGINAL ARTICLE Hand and heart, hand in hand: is radiological hand osteoarthritis associated with atherosclerosis? Ozlem CEMEROGLU, 1 Halil I. AYDIN, 2 Zeynep S. YASAR, 1 Fadime BOZDUMAN, 2 Mustafa SAGLAM, 1 Yusuf SELCOKI, 2 Beyhan ERYONUCU 2 and Hasim CAKIRBAY 1 1 Physical Medicine and Rehabilitation, Turgut Ozal University School of Medicine, and 2 Department of Cardiology, Turgut Ozal University School of Medicine, Ankara, Turkey Abstract Aim: Increasing evidence suggests that atherosclerosis contributes to the initiation or progression of osteoarthritis (OA). It has been suggested that atherosclerosis may cause vascular insufficiency which may lead to or progress OA. In this study, the association between the severity of radiologic hand OA and atherosclerosis was analyzed in women. Methods: Sixty-one women, 50 years of age, free of hand symptoms were enrolled in the study. Posteroanterior views of both hands were obtained using digital radiography. A total of 14 joints were assessed for radiographic OA according to Kellgren/Lawrence (K/L) score. An OA-affected joint was defined as K/L score of 2. Hand OA was defined as 3 joints of both hands affected with OA and severity of hand OA was defined as total K/L scores of all 14 joints of both hands. Gensini scoring was used to evaluate the patients for atherosclerosis severity. Results: The patient characteristics such as presence of diabetes, smoking, hypertension, dyslipidemia and medications used were similar for patients with and without hand OA (P > 0.05) and did not correlate with Gensini or hand OA scores. The mean Gensini scores of patients with hand OA was and without hand OA was (P = 0.017). The degree of osteoarthritic joint involvement and Gensini scores showed a positive correlation (r = 0.332, P = 0.009). Conclusion: Hand OA may be a benign clinical finding that may suggest a possible serious underlying atherosclerosis. Patients with significant hand OA should be screened for atherosclerosis to prevent serious coronary artery disease and related comorbidities. Key words: atherosclerosis, Gensini score, hand osteoarthritis. INTRODUCTION Osteoarthritis (OA) is the most common form of arthritis in older people. The hand is often involved in the process of OA. Depending on the definition of hand OA, the prevalence rates vary. From the radiological point of definition, the prevalence is estimated as high Correspondence: Dr Ozlem Cemeroglu, Assistant Professor, Physical Medicine and Rehabilitation, Turgut Ozal University School of Medicine, Alparslan Turkes Caddesi, No: 57, Emek, Ankara, Turkey. ozlemonur@hotmail.com as 55% in the general population over 70 years of age, whereas symptomatic OA is < 10%. 1 In a few recent studies, it has been suggested that atherosclerosis and OA may be linked. 2 4 It has been suggested that atherosclerosis may cause vascular insufficiency which may lead to or progress OA. 2 Therefore OA may be an important clinical finding suggesting serious underlying atherosclerotic disease. However, there are only a few studies in the literature on atherosclerosis and OA association. In this study, the degree of hand OA and atherosclerosis evaluated by Gensini scoring 5 was analyzed in women 50 years of age or older Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd

2 O. Cemeroglu et al. SUBJECTS AND METHODS Study design A total of 61 women who were 50 years of age, who were scheduled to have coronary angiography for suspected coronary artery disease (CAD) in the Cardiology Department, Turgut Ozal University Hospital, Ankara, Turkey, independent of hand symptoms, were enrolled in the study. Women with a diagnosis of rheumatic diseases, previous hand trauma, finger amputation or hand surgery were excluded. The study was approved by the institutional ethics review committee of the University Hospital. Written informed consent was obtained from all patients prior to enrollment to the study. Coronary angiography was performed by Judkin s technique. Angiographic images were assessed by two independent cardiologists who were blinded to clinical and laboratory findings of the patients. All angiograms were evaluated by Gensini scoring system in terms of severity of coronary stenosis. 5 The severity of CAD was scored as 1 for 1 25% narrowing, 2 for 26 50%, 4 for 51 75%, 8 for 76 90%, 16 for 91 99% and 32 for a completely occluded artery. The Gensini score was assigned based on the degree of luminal narrowing and its regional importance. The regional importance of a coronary artery was designated with a factor. This factor was 5 for left main system lesions, 2.5 for proximal left anterior descending artery and proximal circumflex artery lesions, 1 for distal left anterior descending artery, mid/distal circumflex artery and right coronary artery lesions, and 0.5 for lesions in any other artery branches. The Gensini score was expressed as the sum of the scores of all the coronary arteries. The patient characteristics, medical and laboratory information were obtained during preoperative evaluation, including family history of atherosclerosis, history of previous peripheral/carotid atherosclerotic vascular disease diagnosis, statin use, diagnosis of hypertension, diabetes mellitus, current or past smoking status, use of other medications including betablockers, acetylsalycilate, presence of dyslipidemia, hypercholesterolemia, hypertriglyceridemia. Data were also collected for blood sugar, serum total cholesterol, serum high density lipoprotein (HDL) cholesterol, serum low density lipoptotein (LDL) cholesterol, and serum triglyceride (TG) concentrations from their last visit. Serum levels of total cholesterol of > 200, HDL cholesterol of < 40, LDL cholesterol of > 100 and TG of > 150 were accepted as dyslipidemia. 6 In all 61 patients who were scheduled for coronary angiography, during preoperative work-up, standard postero-anterior views of both hands were obtained using digital radiography. The radiographs were assessed by a single physician blinded to the patients. A total of 14 joints, including the distal interphalangeal (DIP), proximal interphalangeal (PIP), metacarpophalangeal (MCP) and first carpometacarpal (1st CMC) joints of the thumb were assessed for radiographic OA according to the Kellgren/Lawrence (K/L) score. 7 Each of the 28 joints (both hands) examined was scored from 0 to 4, according to the presence and size of osteophyte(s) and to joint space narrowing: 0 represents no OA; 1 = doubtful OA; 2 = definite minimal OA; 3 = moderate OA; 4 = severe OA. An OA-affected joint was defined as K/L score of 2 and hand OA was defined as 3 joints of both hands affected with OA. The severity of hand OA of each participant was indicated with the total K/L scores of all 14 joints of both hands. 8 Statistical analysis Nominal data were expressed as mean SD. Student s t-test was used to compare two sets of data and P-values of < 0.05 were accepted as statistically significant at 95% confidence intervals. The correlation between two variables was assessed using Pearson test. RESULTS The average age of 61 patients included in the study was years (median: 65, range: years). Based on the K/L scoring, 39 patients qualified for diagnosis of hand OA and 22 patients did not. There was no statistically significant difference between the mean ages of the patients with and without hand OA (P = 0.29). All of the patient characteristics, including family history of atherosclerosis, history of previous peripheral/ carotid atherosclerotic vascular disease diagnosis, statin use, diagnosis of hypertension, diabetes mellitus, current or past smoking status, use of other medications including beta-blockers, acetylsalycilate, presence of dyslipidemia, hypercholesterolemia and hypertriglyceridemia were similar in patients with and without hand OA (P > 0.05, Table 1). The mean age, blood glucose concentration, mean serum total cholesterol, serum HDL cholesterol, serum LDL cholesterol and serum TG concentrations were also similar in patients with and without hand OA (P > 0.05, Table 2). 300 International Journal of Rheumatic Diseases 2014; 17:

3 Hand osteoarthritis and atherosclerosis Table 1 Characteristics of patients with and without hand osteoarthritis (OA) Subjects with hand OA (n = 39) Subjects without hand OA (n = 22) n (%) Family history of 5 (12.8) 2 (9.1) atherosclerosis History of peripheral/ 13 (33.3) 7 (31.8) carotid atherosclerotic vascular disease History of: Diabetes mellitus 17 (43.6) 9 (40.9) Hypertension 31 (79.5) 17 (77.3) Smoking (current and 5 (12.8) 4 (18.2) past) Use of beta-blockers 13 (33.3) 8 (36.4) Use of acetylsalycilate 19 (48.7) 12 (54.5) Use of statins 9 (23.1) 8 (36.4) Dyslipidemia* 32 (82.1) 15 (68.2) Hypercholesterolemia 32 (82.1) 15 (68.2) Total cholesterol > (51.3) 8 (36.4) HDL-cholesterol < (46.2) 5 (22.7) LDL-cholesterol > (66.7) 11 (50) Hypertriglyceridemia 20 (51.3) 8 (36.4) *Serum levels of total cholesterol > 200 and/or HDL < 40 and/or LDL > 100 and/or TG > 150. Serum levels of total cholesterol > 200 and/or HDL < 40 and/or LDL > 100. Serum levels of TG > 150. P The mean Gensini score was significantly higher in patients with hand OA compared to patients without hand OA ( vs , respectively, P = 0.017). In addition, a significant positive correlation was found between Gensini score and OA score (r = , P = 0.09, Fig. 1). Gensini scores strongly correlated with age of the patient (r = 0.45, P < 0.01); however, there were no correlations between Gensini scores and all other laboratory measurements, including blood glucose concentration, mean serum total cholesterol, serum HDL cholesterol, serum LDL cholesterol and TG (P > 0.05). There was no correlation between hand OA score and patient age, blood glucose concentration, serum total Figure 1 Correlation between osteoarthritis (OA) score and Gensini score. Table 2 Comparison of the patients with and without hand osteoarthritis (OA) Total subjects (n = 61) Subjects with hand OA (n = 39) Subjects without hand OA (n = 22) P* Mean SD (min max) Mean SD Mean SD Age (years) (50 81) Glucose () (82 328) Cholesterol Total () ( ) HDL () (21 85) LDL () (41 209) Triglycerides () (41 335) Gensini score (1 71) OA score (5 75) < *P-values are between subjects with and without hand OA. International Journal of Rheumatic Diseases 2014; 17:

4 O. Cemeroglu et al. cholesterol, serum HDL cholesterol or serum LDL cholesterol. However, only the correlation between hand OA score and serum TG concentrations was statistically significant (P = 0.041). DISCUSSION The aim of this study was to investigate the association between radiologic hand OA and atherosclerosis in older women. Our results showed that the degree of coronary artery stenosis by Gensini scoring correlated positively with the severity of radiologic hand OA. Osteoarthritis is the most common joint disorder that causes destruction of cartilage and decrease in joint space, resulting in disruption of joint function. The hand is commonly involved in OA and affects daily life of the elderly, causing significant disability. 9 Many risk factors have been suggested for OA, including age and female gender. In the AGES (Age, Gene/ Environment Susceptibility) Reykjavik study on 5342 patients, 10 the prevalence and severity of hand OA were significantly higher in women than men; however, the exact mechanism is unknown. It may be suggested that due to hormonal changes during menopause, women are more at risk of developing vascular disease and OA. However, a systematic review found no clear association between female hormonal aspects and OA. 11 In our study, only female patients over 50 years of age were included due to the prevalence of OA as described earlier. Other potential risk factors besides age and female gender include obesity, diabetes, menopause and hypercholesterolemia, which suggest that OA could be a part of or linked to metabolic syndrome in older people. 12 Furthermore, a higher risk of cardiovascular death has been reported in patients with hip or knee OA. 13 It is also suggested that osteoarthritic changes may be due to vascular changes, including local venous obstruction and hypercoagulability that may alter cartilage nutrition and cause further progression of OA. 14 It is proposed that OA may be primarily an atheromatous vascular disease of subchondral bone. 15 Many epidemiological and imaging studies and use of statins to prevent atherosclerosis showed that atherosclerosis and resulting circulatory compromise may play a role in the pathogenesis of OA In our study, patients with hand OA had a more significant atherosclerosis (higher Gensini score) compared to the patients without hand OA. Furthermore, there was a positive correlation between radiological severity of osteroarthritic joint involvement and severity of atherosclerosis. However, in our study, patient characteristics, including family history of atherosclerosis, history of previous peripheral/carotid atherosclerotic vascular disease diagnosis, statin use, diagnosis of hypertension, diabetes mellitus, current or past smoking status, use of other medications, presence of dyslipidemia, hypercholesterolemia and hypertriglyceridemia, were similar in patients with and without hand OA. No correlation was found between the OA scores and the age, serum glucose, total cholesterol, HDL cholesterol and LDL cholesterol levels. Although the number of patients studied may be a limitation of the study, it may be proposed that there might be an etiological association between OA and atherosclerosis. However, this study is a preliminary report of a possible relation between the severity of radiological hand OA and the degree of atherosclerosis based on the angiographic findings of the patients with suspected coronary artery disease, and further studies will be needed to support our findings. Considering the strong genetic inheritance of hand OA, genetic factors should be kept in mind in etiopathogenesis. The KLOTHO gene, which codes for an anti-aging protein, has recently been implicated both as a susceptibility factor for hand OA in women 19 and as a candidate gene for atherosclerosis. 20 In conclusion, this study reports a positive correlation between the severity of radiologic hand OA and the degree of atherosclerosis in women over 50 years of age. Therefore, hand OA may be suggested as a relatively benign clinical finding that may be a red flag for a possible associated atherosclerosis. Patients with severe hand OA should be screened for atherosclerosis to prevent serious coronary artery disease-related comorbidities. REFERENCES 1 Niu J, Zhang Y, LaValley M et al. (2003) Symmetry and clustering of symptomatic hand osteoarthritis in elderly men and women: the Framingham Study. Rheumatology (Oxford) 42, Jonsson H, Helgadottir GP, Aspelund T et al. (2009) Hand osteoarthritis in older women is associated with carotid and coronary atherosclerosis: the AGES Reykjavik study. Ann Rheum Dis 68, Shirinsky IV, Shirinsky VS (2013) Treatment of erosive osteoarthritis with peroxisome proliferator-activated receptor alpha agonist fenofibrate: a pilot study. Rheumatol Int [Epub ahead of print]. 4 Hoeven TA, Kavousi M, Clockaerts S et al. (2013) Association of atherosclerosis with presence and progression of 302 International Journal of Rheumatic Diseases 2014; 17:

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