Seoyoung C. Kim

Hyperuricemia and Coronary Heart Disease: A Systematic Review and Meta-Analysis

The role of serum uric acid as an independent risk factor for cardiovascular disease remains unclear, although hyperuricemia is associated with cardiovascular disease such as coronary heart disease (CHD), stroke, and hypertension.

Hyperuricemia and incident hypertension: A systematic review and meta‐analysis

A novel rodent model and a recent randomized trial of hyperuricemic adolescents with hypertension suggest a pathogenetic role of uric acid in hypertension, but it remains unknown whether these findings would be applicable to adult populations where the larger disease burden exists. We conducted a systematic review and meta‐analysis to determine if hyperuricemia was associated with incident hypertension, particularly in various demographic subgroups.

Hyperuricemia and Risk of Stroke: A Systematic Review and Meta-analysis

OBJECTIVE To assess the association between hyperuricemia and risk of stroke incidence and mortality because hyperuricemia is hypothesized to be a risk factor for stroke and other cardiovascular disease, but, to date, results from observational studies are conflicting. METHODS A systematic review and meta-analysis were conducted. Studies were identified by searching major electronic databases using the Medical Subject Headings and keywords without restriction in languages. Prospective cohort studies were included only if they contained data on stroke incidences or mortalities related to serum uric acid levels in adults. Pooled risk ratios (RRs) for the association of stroke incidence and mortality with serum uric acid levels were calculated. RESULTS A total of 16 studies including 238,449 adults were eligible and abstracted. Hyperuricemia was associated with a significantly higher risk of both stroke incidence (6 studies; RR 1.41, 95% confidence interval [95% CI] 1.05, 1.76) and mortality (6 studies; RR 1.36, 95% CI 1.03, 1.69) in our meta-analyses of unadjusted study estimates. Subgroup analyses of studies adjusting for known risk factors such as age, hypertension, diabetes mellitus, and cholesterol still showed that hyperuricemia was significantly associated with both stroke incidence (4 studies; RR 1.47, 95% CI 1.19, 1.76) and mortality (6 studies; RR 1.26, 95% CI 1.12, 1.39). The pooled estimate of multivariate RRs did not differ significantly by sex. CONCLUSION Hyperuricemia may modestly increase the risks of both stroke incidence and mortality. Future research is needed to determine whether lowering uric acid level has any beneficial effects on stroke.

Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: a systematic review and meta-analysis

Although there is strong evidence that bisphosphonates prevent certain types of osteoporotic fractures, there are concerns that these medications may be associated with rare atypical femoral fractures (AFF). Recent published studies examining this potential association are conflicting regarding the existence and strength of this association. We conducted a systematic review and meta‐analysis of published studies examining the association of bisphosphonates with subtrochanteric, femoral shaft, and AFF. The random‐effects model was used to calculate the pooled estimates of adjusted risk ratios (RR). Subgroup analysis was performed by study design, for studies that used validated outcome definitions for AFF, and for studies reporting on duration of bisphosphonate use. Eleven studies were included in the meta‐analysis: five case‐control and six cohort studies. Bisphosphonate exposure was associated with an increased risk of subtrochanteric, femoral shaft, and AFF, with adjusted RR of 1.70 (95% confidence interval [CI], 1.22–2.37). Subgroup analysis of studies using the American Society for Bone and Mineral Research criteria to define AFF suggests a higher risk of AFF, with bisphosphonate use with RR of 11.78 (95% CI, 0.39–359.69) as compared to studies using mainly diagnosis codes (RR, 1.62; 95% CI, 1.18–2.22), although there is a wide confidence interval and severe heterogeneity (I2 = 96.15%) in this subgroup analysis. Subgroup analysis of studies examining at least 5 years of bisphosphonate use showed adjusted RR of 1.62 (95% CI, 1.29–2.04). This meta‐analysis suggests there is an increased risk of subtrochanteric, femoral shaft, and AFF among bisphosphonate users. Further research examining the risk of AFF with long‐term use of bisphosphonates is indicated as there was limited data in this subgroup. The public health implication of this observed increase in AFF risk is not clear.

Risk of osteoporotic fracture in a large population-based cohort of patients with rheumatoid arthritis.

IntroductionAlthough osteoporosis has been reported to be more common in patients with rheumatoid arthritis (RA), little is known whether the risk of osteoporotic fractures in these patients differs by age, sex, and anatomic site.MethodsA retrospective cohort study was conducted using a health care utilization database. Incidence rates (IRs) and rate ratios (RRs) of osteoporotic fractures with 95% confidence intervals (CIs) were calculated. Multivariable Cox proportional hazards models compared the risk of osteoporotic fracture at typical sites between RA and non-RA patients.ResultsDuring a median 1.63-year follow-up, 872 (1.9%) of 47,034 RA patients experienced a fracture. The IR for osteoporotic fracture at typical sites among RA patients was 9.6 per 1,000 person-years, 1.5 times higher than the rate of non-RA patients. The IR was highest for hip fracture (3.4 per 1,000 person-years) in RA. The IRs across all age groups were higher for women than men and increased with older age in both groups. The RRs were elevated in RA patients across all common sites of osteoporotic fracture: hip (1.62, 95% CI 1.43 to 1.84), wrist (1.15, 95% CI 1.00 to 1.32), pelvis (2.02, 95% CI 1.77 to 2.30), and humerus (1.51, 95% CI 1.27 to 1.84). After confounding adjustment, a modest increase in risk for fracture was noted with RA (hazard ratio 1.26, 95% CI 1.15 to 1.38).ConclusionsOur study showed an increased risk of osteoporotic fractures for RA patients across all age groups, sex and various anatomic sites, compared with non-RA patients.

Tumor necrosis factor blockade and the risk of viral infection

Tumor necrosis factor (TNF) blockers are widely used to treat rheumatoid arthritis and other chronic inflammatory diseases. Many studies have demonstrated an increased risk of opportunistic infections such as tuberculosis and fungal infection in patients treated with TNF blockers, which is thought to be related to the primary role of TNF both in host defense and in the immune response. Little is known, however, about the association between TNF blockade and the development of viral infection. Owing to the critical role of TNF in the control of viral infection, depletion of this cytokine with TNF blockers could facilitate the development or reactivation of viral infection. A number of large observational studies have found an increased risk of herpes zoster in patients receiving TNF blockers for the treatment of rheumatoid arthritis. This Review draws attention to the risk of several viral infections, including HIV, varicella zoster virus, Epstein–Barr virus, cytomegalovirus, and human papillomavirus, in patients receiving TNF-blocking therapy for chronic inflammatory conditions. In addition, implications for clinical practice and possible preventative approaches are discussed.

Oral bisphosphonates and risk of subtrochanteric or diaphyseal femur fractures in a population‐based cohort

Bisphosphonates are the primary therapy for postmenopausal and glucocorticoid‐induced osteoporosis. Case series suggest a potential link between prolonged use of bisphosphonates and low‐energy fracture of subtrochanteric or diaphyseal femur as a consequence of oversuppression of bone resorption. Using health care utilization data, we conducted a propensity score–matched cohort study to examine the incidence rates (IRs) and risk of subtrochanteric or diaphyseal femur fractures among oral bisphosphonate users compared with raloxifene or calcitonin users. A Cox proportional hazards model evaluated the risk of these fractures associated with duration of osteoporosis treatment. A total of 104 subtrochanteric or diaphyseal femur fractures were observed among 33,815 patients. The estimated IR of subtrochanteric or diaphyseal femur fractures per 1000 person‐years was 1.46 [95% confidence interval (CI) 1.11–1.88] among the bisphosphonate users and 1.43 (95% CI 1.06–1.89) among raloxifene/calcitonin users. No significant association between bisphosphonate use and subtrochanteric or diaphyseal femur fractures was found [hazard ratio (HR) = 1.03, 95% CI 0.70–1.52] compared with raloxifene/calcitonin. Even with this large study size, we had little precision in estimating the risk of subtrochanteric or diaphyseal femur fractures in patients treated with bisphosphonates for longer than 5 years (HR = 2.02, 95% CI 0.41–10.00). The occurrence of subtrochanteric or diaphyseal femur fracture was rare. There was no evidence of an increased risk of subtrochanteric or diaphyseal femur fractures in bisphosphonate users compared with raloxifene/calcitonin users. However, this study cannot exclude the possibility that long‐term bisphosphonate use may increase the risk of these fractures.

Thromboprophylaxis for patients with cancer and central venous catheters: a systematic review and a meta-analysis.

Central venous catheter (CVC) placement increases the risk of thrombosis and subsequent death in patients with cancer. The objective of this systematic review was to determine the efficacy and safety of anticoagulation in reducing mortality and thromboembolic events in cancer patients with a CVC.

Risk of high-grade cervical dysplasia and cervical cancer in women with systemic inflammatory diseases: a population-based cohort study

Background Previous studies have suggested a potential risk of cervical cancer in patients with systemic inflammatory diseases (SID) such as inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE). Objectives To assess the risk of high-grade cervical dysplasia, a surrogate endpoint for cervical cancer and cervical cancer, in women with SID, including IBD, psoriasis, rheumatoid arthritis (RA) or SLE, compared with the risk in women without SID. Methods Using US insurance data (2001–2012), we conducted a cohort study of 133 333 women with SID, based on two or more diagnoses and one or more dispensed prescription for disease-specific treatment, and 533 332 women without SID. High-grade cervical dysplasia and cervical cancer was defined by a validated algorithm with a positive predictive value of ≥81%. Results Over the mean follow-up of 2.1 years, the crude incidence rate of high-grade cervical dysplasia and cervical cancer per 100 000 person-years was the highest at 141.1 in SLE and the lowest at 82.2 in psoriasis among women with SID, and 73.4 in women without SID. The multivariable HR adjusted for potential confounders was 1.07 (95% CI 0.79 to 1.45) in IBD, 0.96 (95% CI 0.73 to 1.27) in psoriasis, 1.49 (95% CI 1.11 to 2.00) in RA and 1.53 (95% CI 1.07 to 2.19) in SLE. Multivariable HRs were increased, but not statistically significant, in IBD, RA and SLE with baseline use of systemic immunosuppressive drugs or steroids. Conclusions The risk of high-grade cervical dysplasia and cervical cancer was 1.5 times higher in women with RA and SLE than in those without SID. The risk may be increased in IBD with use of systemic immunosuppressive drugs or steroids.

Serious Infections Among Adult Medicaid Beneficiaries With Systemic Lupus Erythematosus and Lupus Nephritis

To examine the epidemiology of serious infections, a significant cause of morbidity and mortality in systemic lupus erythematosus (SLE), in a nationwide cohort of SLE and lupus nephritis (LN) patients.