Gouty Arthritis: Krishnan E

Krishnan E. · S709 BST South, 3500 Terrace Street, Pittsburgh, PA 15215, USA. · Curr Rheumatol Rep. · Pubmed #18638434 No free full text.

Abstract: Gout is the leading cause of inflammatory arthritis, typically affecting men and characterized by intermittent, abrupt onset of intense inflammation. The association between gout, atherosclerosis, and vascular disease has been noted in medical literature since the end of the 19th century, yet it has not been well studied. This review critically appraises the few epidemiologic studies that ask if gout is a risk factor for coronary artery disease. An exhaustive literature search using search engines and cross-referencing found four major studies and several smaller studies that have evaluated gout as a risk factor for coronary artery disease. The available studies were too heterogeneous to permit formal meta-analysis. Although there are gaps in evidence pointing to a causative pathway, overall, evidence exists for a relationship between gouty arthritis and coronary artery disease independent of traditional risk factors.

Avram Z, Krishnan E. · Division of Rheumatology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. · Rheumatology (Oxford). · Pubmed #18443007 No free full text.

Abstract: Rheumatologists care for patients with gouty arthritis, a condition caused by chronic and uncontrolled hyperuricaemia. Hyperuricaemia, gout and renal dysfunction are often bedfellows, raising the possibility of the former causing the latter. We sought the answer to the question 'Among patients with normal measures of glomerular filtration, does hyperuricaemia predict future renal disease'? We identified prospective cohort studies evaluating the relationship between serum uric acid and chronic kidney function from the past 20 yrs, through MEDLINE, Cochrane Library and EMBASE searches and bibliography cross-referencing. Nine cohort studies that met the selection criteria were found. Because of the extreme heterogeneity, a statistical meta-analysis was not performed. Most (eight out of nine) studies found an independent risk factor for deterioration of kidney function. Nearly all published prospective studies support the role of hyperuricaemia as an independent risk factor for renal dysfunction. In the absence of large randomized controlled trials of uric acid reduction, it remains uncertain if this relation is causal or merely an epiphenomenon. Regardless, our review suggests that hyperuricaemia is a useful, inexpensively measured, widely available and useful early marker for chronic kidney disease.

Krishnan E, Svendsen K, Neaton JD, Grandits G, Kuller LH, Anonymous00205. · Division of Rheumatology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. · Arch Intern Med. · Pubmed #18504339 links to  free full text

Abstract: BACKGROUND: There are limited data available on the association of gouty arthritis (gout) in middle age with long-term cardiovascular disease (CVD) mortality. METHODS: We performed a 17-year follow-up study of 9105 men, aged 41 to 63 years and at above-average risk for coronary heart disease, who were randomized to the Multiple Risk Factor Intervention Trial and who did not die or have clinical or electrocardiographic evidence of coronary artery disease during the 6-year trial. Risk of CVD death and other causes subsequent to the sixth annual examination associated with gout was assessed by means of Cox proportional hazards regressions. RESULTS: The unadjusted mortality rates from CVD among those with and without gout were 10.3 per 1000 person-years and 8.0 per 1000 person-years, respectively, representing an approximately 30% greater risk. After adjustment for traditional risk factors, use of diuretics and aspirin, and serum creatinine level, the hazard ratio (gout vs no gout) for coronary heart disease mortality was 1.35 (95% confidence interval [CI], 1.06-1.72). The hazard ratio for death from myocardial infarction was 1.35 (95% CI, 0.94-1.93); for death from CVD overall, 1.21 (95% CI, 0.99-1.49); and for death from any cause, 1.09 (95% CI, 1.00-1.19) (P = .04). The association between hyperuricemia and CVD was weak and did not persist when analysis was limited to men with hyperuricemia without a diagnosis of gout. CONCLUSION: Among middle-aged men, a diagnosis of gout accompanied by an elevated uric acid level imparts significant independent CVD mortality risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000487.

Wu EQ, Patel PA, Yu AP, Mody RR, Cahill KE, Tang J, Krishnan E. · Analysis Group, 111 Huntington Ave, 10th Fl., Boston, MA 02199,USA. ewu@analysisgroup · J Manag Care Pharm. · Pubmed #18331118 links to  free full text

Abstract: BACKGROUND: Gout is a common cause of inflammatory arthritis in the United States, and its prevalence has increased in recent decades, especially among older adults. Older adults with gout are of particular interest because they tend to experience higher rates of tophi, an advanced stage of gout, than do younger patients. OBJECTIVE: For older adults with gout to (1) assess health care utilization and costs from a third-party payer perspective; (2) evaluate health care costs related to tophi; and (3) explore the relationship between elevated serum uric acid (UA) level, an indicator of disease control, and health care utilization. METHODS: Data were extracted from the Integrated Healthcare Information Services (IHCIS) claims database (1999-2005), which includes approximately 40 private health plans in the United States for approximately 13 million beneficiaries, about 4% of whom are aged 65 years or older. Patients were included in the study if they: (1) had 2 diagnoses of gout (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code of 274.xx) on separate medical claims or 1 gout diagnosis plus at least 1 gout-related pharmacy claim (i.e., allopurinol, probenecid, colchicines, or sulfinpyrazone); (2) were at least 65 years old at the first diagnosis date (study index date); and (3) had 1 year of continuous eligibility both before and after the study index date. A comparison sample of elderly members without gout was selected using a 1:1 match to gout patients based on age, gender, and geographic region. Individuals in the comparison group also had 1 year of continuous eligibility both before and after the study index date, defined as the same index date as the respective matched gout patient. Patients with possible tophi were identified from at least 1 medical claim with an ICD-9-CM code 274.8x (274.81=gouty tophi of the ear; 274.82 = gouty tophi of other sites except ear; 274.89 = gout with other specified manifestations) during the 12-month study period following the study index date. Additionally, a subgroup of gout patients with at least 1 serum UA measure was selected. Patients were divided into 3 groups according to their serum UA level on the earliest test date (serum UA index date): low (< 6 mg per dL), moderate-high (6-8.99 mg per dL), and very high (> or = 9 mg per dL). Health care utilization was categorized into inpatient services, outpatient services, emergency room services, other medical services, and use of prescription drugs. Medical services were classified by the place of service indicated in the claim. Medical services costs and pharmacy costs were defined as the amount paid to the provider plus member cost share (e.g., deductible, copayment). Two types of costs were assessed in the analysis: total all-cause health care costs and gout-related costs, defined as costs associated with a claim with a primary or secondary diagnosis of gout (ICD-9-CM code 274.xx). Differences in total all-cause health care costs were calculated by comparing (1) gout patients and gout-free members during the 12-month period following the study index date; (2) gout patients with and without tophi during the 12-month period following the study index date; and (3) gout patients across the 3 serum UA categories during the 12-month period following the serum UA index date. Multivariate regression analyses were used to control for patients' baseline demographics, prior comorbidities indicated by the Deyo-Charlson Comorbidity Index, and number of medications used during the 12 months prior to the study index date. RESULTS: Over the 7 years of claims data through 2005, there were 11,935 gout patients aged 65 years or older. The sample had an average age of 71.4 years and was predominantly male (73.5%). In the 12 months following the study index date, the mean unadjusted per-patient gout-related health care cost was $876 (standard deviation $3,373) in 2005 dollars, 5.9% of the total all-cause health care cost of $14,734 (SD $27,401) for gout patients. Unadjusted total 12-month all-cause health care cost for the gout-free members was $9,219 (SD $20,186). After statistical adjustment for comorbidities, the difference in total 12-month all-cause health care costs between gout patients and gout-free members was $3,038 (P < 0.001). A diagnosis suggesting possible tophi was found in 2.0% (n = 240) of gout patients in the sample. After statistical adjustment for comorbidities, the difference in total 12-month all-cause health care costs between gout patients with and without tophi was $5,501 (P < 0.001), and the difference in total adjusted 12-month gout-related costs between patients with and without tophi was $1,710 (P < 0.001). Among the 2,237 (18.7%) patients with at least 1 serum UA measure, 28.3% had a low serum UA level, 52.4% had a moderate-high serum UA level, and 19.3% had a very high serum UA level. For patients with low, moderate-high, and very high serum UA levels, regression-adjusted gout-related costs in the 12 months following the serum UA index date represented, respectively, 2.9%, 2.7%, and 3.9% of total regression-adjusted health care costs. The group with a very high serum UA level had significantly higher regression-adjusted total 12-month all-cause health care costs and gout-related costs compared with those with a low serum UA level ($3,103 and $276 higher, respectively). CONCLUSIONS: Elderly patients with a diagnosis of gout have higher all-cause health care utilization and costs compared with matched elderly patients without a diagnosis of gout. Gout-related costs represent about 6% of total health care costs in elderly patients with gout. Very high serum UA levels (i.e., > or = 9 mg per dL) and diagnoses suggesting possible tophi are associated with increased utilization and costs in elderly gout patients.

Krishnan E, Lienesch D, Kwoh CK. · Division of Rheumatology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. · J Rheumatol. · Pubmed #18260174 No free full text.

Abstract: OBJECTIVE: To describe the ambulatory care utilization by patients with gouty arthritis (gout) in the United States using a nationally representative sample. METHODS: A cross-sectional survey design based on the ambulatory care data from the 2002 US National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey was used to examine the ambulatory care burden for gout, the characteristics of gout patients, the types of providers who see gout patients, and prescribing patterns associated with the management of gout. Weighted analyses were performed to estimate the effect of age, sex, and ethnicity on the association with gout and prescription of allopurinol. RESULTS: Of the 973 million ambulatory care visits in the United States, 3.9 million were for gout. The majority of visits were for men. The average age for men with gout was lower than that for women with gout (65 vs 70 years of age). Over two-thirds of these gout visits were attended to by primary care providers, whereas visits to rheumatologists constituted only a very small proportion of these visits (1.3%). There were 2.8 million prescriptions for allopurinol, 700,000 prescriptions for nonsteroidal antiinflammatory drugs, 381,000 prescriptions for colchicine, and 341,000 prescriptions for prednisone. After adjusting for age and sex, Asians were 2.7 times more likely than Caucasians to have a gout visit. Yet these patients had lower probability of receiving allopurinol (odds ratio 0.04, 95% confidence interval 0.01-0.27). CONCLUSION: The majority of patients with gout are seen by generalist physicians. Asian ethnicity is associated with higher number of visits for gout, but a lower frequency of allopurinol treatment.

Baker JF, Schumacher HR, Krishnan E. · Department of Medicine, University of Pennsylvania, USA. · Angiology. · Pubmed #17875958 No free full text.

Abstract: Although several studies report an association between hyperuricemia and coronary artery disease, little is known about the effect of hyperuricemia and gout on the risk of peripheral arterial disease (PAD). Data on 283 incident clinical cases of PAD during a randomized controlled trial of multiple cardiovascular risk factor intervention are evaluated. The serum uric acid levels among these individuals are compared with those of individuals who did not develop PAD during the study period. Multivariate logistic regression analyses measure the risk of developing PAD associated with higher levels of serum uric acid after adjusting for the effect of traditional vascular risk factors. Age and smoking are independently associated with development of PAD, with odds ratios of 1.08 (95% confidence interval [CI], 1.06-1.09) and 3.83 (95% CI, 2.49-5.91) per year, respectively. Hyperuricemia (serum uric acid level, >7.0 mg/dL) is an independent risk factor, with an odds ratio of 1.23, but the confidence interval of the estimate is wide (95% CI, 0.98-1.54). In this multivariate model, a history of gout was associated with an odds ratio of 1.33 (95% CI, 1.07-1.66). Serum uric acid level is independently associated with a higher (but statistically nonsignificant) risk of PAD. A history of gouty arthritis is an independent and statistically significant predictor of incidence of PAD even after adjustment for the effect of underlying hyperuricemia.

Krishnan E, Baker JF, Furst DE, Schumacher HR. · University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. · Arthritis Rheum. · Pubmed #16871533 links to  free full text

Abstract: OBJECTIVE: To determine if hyperuricemia and gouty arthritis are independent risk factors for acute myocardial infarction (MI) and, if so, whether they are independent of renal function, diuretic use, metabolic syndrome, and other established risk factors. METHODS: We performed multivariable logistic and instrumental variable probit regressions on data from the Multiple Risk Factor Intervention Trial (MRFIT). RESULTS: Overall, there were 12,866 men in the MRFIT who were followed up for a mean of 6.5 years. There were 118 events of acute MI in the group with gout (10.5%) and 990 events in the group without gout (8.43%; P = 0.018). Hyperuricemia was an independent risk factor for acute MI in the multivariable regression models, with an odds ratio (OR) of 1.11 (95% confidence interval [95% CI] 1.08-1.15, P < 0.001). In multivariable regressions in which the above risk factors were used as covariates, gout was found to be associated with a higher risk of acute MI (OR 1.26 [95% CI 1.14-1.40], P < 0.001). Subgroup analyses showed that a relationship between gout and the risk of acute MI was present among nonusers of alcohol, diuretics, or aspirin and among those who did not have metabolic syndrome, diabetes mellitus, or obesity. In separate analyses, a relationship between gout and the risk of acute MI was evident among those with and without those hyperuricemia. CONCLUSION: The independent risk relationship between hyperuricemia and acute MI is confirmed. Gouty arthritis is associated with an excess risk of acute MI, and this is not explained by its well-known links with renal function, metabolic syndrome, diuretic use, and traditional cardiovascular risk factors.