Effect of colchicine, methotrexate, and hydroxychloroquine therapy on cardiovascular outcomes in patients with calcium pyrophosphate crystal deposition disease

Anti-inflammatory therapy, such as colchicine (COL), has been suggested to affect the incidence of cardiovascular events in patients with calcium pyrophosphate crystal deposition disease (CPPD).Objective: to study the effect of anti-inflammatory therapy with COL, hydroxychloroquine (HC), and methotrexate (MT) on cardiovascular outcomes in patients with CPPD.Patients and methods. The study included 305 patients with CPPD, the majority (62.30%) were women. The average follow-up period was 3.9±2.7 years. Among factors influencing cardiovascular outcome were considered: gender; age; smoking; alcohol intake >20 conventional doses per week; arterial hypertension; a history of cardiovascular diseases (CVD), in particular ischemic heart disease, acute myocardial infarction, acute cerebrovascular accident, chronic heart failure >III stage according to NYHA, as well as type 2 diabetes mellitus (DM); body mass index >25 kg/m2 and >30 kg/m2; cholesterol level (CHOL) >5.1 mmol/l; glomerular filtration rate (GFR) < 60 ml/min/1.73 m2; serum uric acid level >360 μmol/l; hypercalcemia (serum calcium level >2.62 mmol/L); CRP level >2 mg/l; the presence of hyperparathyroidism (parathyroid hormone level >65 pg/ml); CPPD phenotypes (asymptomatic, osteoarthritis with calcium pyrophosphate crystals, chronic arthritis, acute arthritis); intake of COL, HC, MT, glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs).Results and discussion. 264 patients were under dynamic observation. Any of the studied cardiovascular events were registered in 79 (29.9%) patients. During the observation period, 46 (17.4%) patients died, in 76.1% of cases the cause of death was CVD. Death from other causes was diagnosed in 11 (23.9%) patients. Non-fatal cardiovascular events were reported in 44 (16.7%) cases. The risk of cardiovascular events was higher in patients over 65 years of age (odds ratio, OR 5.97; 95% confidence interval, CI 3.33–10.71), with serum cholesterol levels ≥5.1 mmol/L (OR 1,95; 95% CI 1.04–3.65), GFR <60 ml/min/1.73 m2 (OR 2.78; 95% CI 1.32–5.56), history of CVD (OR 2,32; 95% CI 1.22–4.44). COL therapy reduced the risk of cardiovascular events (OR 0.20; 95% CI 0.11–0.39).Conclusion. Poor CVD outcomes in CPPD are associated with age, hypercholesterolemia, chronic kidney disease, and a history of CVD. The use of COL, in contrast to MT and HC, was accompanied by a decrease in cardiovascular risk.

The prevalence of subclinical atherosclerosis of carotid arteries in patients with calcium pyrophosphate crystal deposition disease and osteoarthritis (pilot study)

To this date there have been no studies of subclinical atherosclerosis in the patients with calcium pyrophosphate crystal deposition disease (CPPD); in osteoarthritis (OA) such works are rare.Objective: to assess the prevalence of subclinical atherosclerosis of carotid arteries (CA) in patients with CPPD and OA.Patients and methods. The case-control study included 26 patients with CPPD and OA. The diagnosis of CPPD was based on the criteria of D.J. McCarty, diagnosis of OA was based on national clinical practice guidelines. We recorded data on smoking, blood pressure level. Assessed blood lipid spectrum, serum levels of glucose, creatinine, uric acid, CRP. Obesity was diagnosed in accordance with the WHO recommendations. All patients underwent CA Doppler ultrasonography (DUS). An increase in intima-media thickness (IMT) >0.9 mm was considered a manifestation of subclinical atherosclerosis. The SCORE index was calculated for all patients.Results and discussion. The median serum CRP level was comparable in CPPD and OA. The CRP level >5 mg/L was detected in 8 patients with CPPD and in 3 patients with OA (p=0.09). Initial signs of atherosclerosis were present in 11 (42%) patients with CPPD and in 8 (31%) patients with OA (p=0.39). In CPPD, an increase in IMT was associated with a CRP level of ≥5 mg/L in 19% of cases, and in OA – in 12.5% (p=0.08). An increase in IMT >1.3 mm was not found in patients of both groups.Conclusion. In patients with CPPD and OA, subclinical atherosclerosis is often present according to the CA ultrasound. Early detection of uncomplicated subclinical atherosclerosis in CPPD and OA is necessary for timely initiation of treatment aimed to prevent the progression of atherosclerosis and the development of cardiovascular diseases.

Hydroxyapatite crystal deposition disease around the hip: a rare cause of piriformis syndrome and ischiofemoral impingement

Hydroxyapatite crystal deposition disease (HADD) around the hip is typically described involving the gluteal tendons. However, HADD can occur in any location and result in varied clinical presentations. Even with small deposits, symptoms can be significant and imaging findings may appear aggressive, mimicking infection and malignancy particularly when in an atypical location. We illustrate cases of both common and rare locations of HADD around the hip, in particular presenting as greater trochanteric pain syndrome, piriformis syndrome and ischiofemoral impingement. The latter two manifestations have not been previously described in the literature. Low signal deposits were identified on MRI at the greater trochanter (gluteus medius tendon), proximal piriformis (adjacent to the sciatic nerve), and quadratus femoris (in the ischiofemoral space), respectively. Associated inflammatory changes with tendinopathy, bursitis and oedema were also demonstrated. The patient with piriformis syndrome underwent steroid injections and shockwave therapy with significant symptom improvement. HADD should be within the differential diagnosis for hip pain and nerve compression syndromes. Knowledge of tendon anatomy and correlation with radiographs or CT, even after MRI, is crucial in recognising unusual manifestations and preventing unnecessary investigation. Therefore, we review the spectrum of imaging features of HADD, as well as the current evidence on its management, to confidently diagnose this condition.

Calcification of coronary arteries in patients with calcium pyrophosphate crystal deposition disease and knee osteoarthritis

The frequency of vascular calcification in patients with osteoarthritis (OA) and calcium pyrophosphate crystal deposition disease (CPPD) has not yet been studied, and the role of calcium crystals (basic and pyrophosphates) in the development of calcification is also unknown.Objective. Determine the presence and degree of calcification of the coronary vessels in patients with calcium pyrophosphate crystal deposition disease and osteoarthritis of the knee joints with no clinical signs of cardiovascular diseases.Materials and methods. One-stage, single-center study, performed by the “case – control” method. The main group – 20 patients with CPPD, the comparison group – 20 patients with OA of the knee joints. Inclusion criteria: age from 18 to 65 years; absence of clinical signs of cardiovascular disease at the time of examination and indications of a history of cardiovascular accidents. Exclusion criteria: unsigned informed consent; pregnancy; breastfeeding; other rheumatic disease; cancer; high and very high cardiovascular risk on the SCORE scale. The survey included an assessment of anthropometric data, blood pressure (BP), lipid profile, serum levels of glucose, creatinine, uric acid, C-reactive protein, vitamin D, osteoprotegerin, parathyroid hormone, and the levels of magnesium, phosphorus, and total calcium were studied. All patients underwent multispiral computed tomography with determination of calcium count and the number of affected arteries. To calculate the coronary score, the A.S. Agatston et al.Results and discussion. Most of the parameters in the compared groups did not differ. When assessing the calcification of the coronary arteries according to the A.S. Agatston et al. 9 (45%) patients with CPPD and 8 (40%) patients with OA had a coronary calcium score >1. Quantitative indicators of calcium score can correspond to coronary artery stenosis ≥20% in 8 (40%) patients with CPPD and in 5 (25%) patients with OA according to J.A. Rumberger et al. The serum level of osteoprotegerin was significantly higher in patients with a calcium score ≥27 according to J.A. Rumberger et al. (p=0.04). Calcification was detected in 9 (56%) of 16 patients with serum vitamin D levels <30 ng/ml and in 8 (33%) of 24 patients with serum vitamin D levels >30 ng/ml.Conclusions. In patients with an initially low cardiovascular risk, the probability of a combination of chondrocalcinosis and cardiovascular calcification is 45%, in OA it is 40%. The risk factors for coronary calcification in patients with CPPD and OA should be studied further.

AB0640 MORTALITY IN CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION DISEASE: PRELIMINARY DATA

Background:Calcium pyrophosphate crystal deposition disease (CPPD) is associated with a high frequency of comorbidities and vascular calcification [1], but it is unknown whether these factors affect cardiovascular mortality.Objectives:To study the structure of mortality in patients with CPPD and compare with the structure of mortality in the Russian Federation.Methods:217 patients with crystal-verified diagnosis of CPPD (McCarty criteria) were included in the prospective study, aged ≥18 years, mean age 59.2 ± 12.6 years, 82 (38%) men and 134 (62%) women. The median follow-up was 3.9 [1.9; 7.2] years, patients were followed up for at least a year. The exclusion criteria are the presence of other rheumatic diseases with arthritis symptoms. The examination of patients included the history taking, assessment of anthropometric parameters, the presence of comorbidity and the following laboratory tests: determination of serum creatinine level (with calculation of glomerular filtration rate (eGFR) using the MDRD formula), total cholesterol (TC), C-reactive protein (CRP). Statistica 12.0 package was used for statistical data processing.Results:A total of 217 patients were included. Arterial hypertension was detected in 115 (53%) patients, coronary heart disease in 51 (24%) patients, diabetes mellitus in 26 (12%) patients, chronic renal failure in 17 (8%) patients, hyperparathyroidism in 18 (8%) patients, chronic heart failure in 22 (10%) patients. 65 (30%) patients had a family history for CVD, 31 (14%) patients were smokers. 122 (56%) patients had an increased level of total cholesterol> 5.0 mmol/L and 54 (25%) patients – the level of CRP>5 mg/L.23 (11%) patients, 12 (52%) men and 11 (48%) women, died, the average age of the deceased being 62.7±9.2 years. In 15 (65%) cases out of 23, death occurred due to cardiovascular complications, which is higher than the cardiovascular mortality rate in the Russian Federation (53%). Among CVD, the distribution was as follows: acute myocardial infarction - 6 (40%) patients,apoplectic attack - 5 (33) patients, thrombosis - 2 (13%) patients, rhythm disturbances – 1 (7%) patient and decompensation of chronic heart failure - 1 (7%) patient.Conclusion:CVD is the main cause of death in patients with CPPD and the total frequency of mortality from CVD exceeds the population one. Further research is needed, including studies of the risk factors for overall and cardiovascular mortality in patients with CPPD.References:[1]Abhishek A, Doherty S, Maciewicz R, et al. Association between low cortical bone mineral density, soft-tissue calcification, vascular calcification and chondrocalcinosis: a case-control study. Ann Rheum Dis. 2013;73(11):1997-2002. doi: 10.1136/annrheumdis2013-203400Disclosure of Interests:Maxim Elisеev Speakers bureau: Berlin Chemie Menarini Group, Novartis International AG, EGIS, Aleksandra Novikova: None declared., Olga Sheliabina: None declared., Maria Chikina: None declared.