Faculty Bibliography

BACKGROUND:Kidney transplantation (KT) is a life-prolonging therapy in certain older end-stage renal disease patients, but concerns regarding peritransplantation morbidity remain. We estimate the relative increase in time spent hospitalized in the year post-KT for older versus younger end-stage renal disease patients. METHODS:This was a retrospective analysis of 27,247 Medicare-primary KT recipients from 2000 to 2005 using United States Renal Data System and Organ Procurement and Transplantation Network data. Time spent hospitalized was enumerated in the year pre-KT and post-KT from Medicare Part A claims. Excess inpatient days were the difference in an individual's post-KT and pre-KT hospital and skilled nursing facility days, standardized by time spent alive in the year post-KT. RESULTS:The median excess inpatient days were similar by age group (9 in recipients 65 years or older vs. 7 in recipients younger than 65 years); however, the distribution was skewed, such that many more older adults had large increases in inpatient time (8.6% totaled >120 excess inpatient days vs. 4.2% in younger recipients). Among older recipients, risk factors for poor outcomes included recipient age, donor age, longer dialysis vintage, diabetic nephropathy, and congestive heart failure. Reasons for posttransplantation hospitalization were similar by age with the exception of rehabilitation, which was common only in the 65+ age group. Mean inpatient costs were equivalent pretransplantation by age but significantly higher posttransplantation among older KT recipients. CONCLUSIONS:Posttransplantation morbidity may not be so different in most of the older individuals selected for KT; however, a minority fares much worse.

The authors quantified the impact of hypertension on gout incidence in middle-aged white and African American men and women. The Atherosclerosis Risk in Communities Study (ARIC) was a prospective population-based cohort that recruited patients between 1987 and 1989 from 4 US communities. Using a time-dependent Cox proportional hazards model, the authors estimated the adjusted hazard ratio (HR) of incident gout by time-varying hypertension and tested for mediation by serum urate level. There were 10,872 participants among whom 45% had hypertension during follow-up; 43% were men and 21% were African American. Over 9 years, 274 (2.5%) participants developed gout (1.8% of women and 3.5% of men). The unadjusted HR of incident gout was approximately 3 times (HR, 2.87; 95% confidence interval [CI], 2.24-3.78) greater for those with hypertension. Adjusting for confounders resulted in an attenuated but still significant association between hypertension and gout (HR, 2.00; 95% CI, 1.54-2.61). Adjustment for serum urate level further attenuated but did not abrogate the association (HR, 1.36, 95% CI, 1.04-1.79). There was no evidence of effect modification by sex (P=.35), race (P=.99), or obesity at baseline (P=.82). Hypertension was independently associated with increased gout risk in middle-aged African American and white adults. Serum urate level may be a partial intermediate on the pathway between hypertension and gout.

INTRODUCTION/BACKGROUND:There is a growing prevalence of gout in the US and worldwide. Gout is a recognized risk factor for cardiovascular disease (CVD). It is unclear whether other risk factors for CVD are also associated with increased risk of gout. Anemia is one such CVD risk factor. No studies have evaluated the relationship between anemia and gout. We tested whether anemia was associated with incident gout independent of comorbid conditions in Atherosclerosis Risk in the Communities. METHODS:This population-based cohort recruited 15,792 individuals in 1987 to 1989 from four US communities and contained nine years of follow-up. Anemia was defined as hemoglobin <13.5 g/dL for men and <12 g/dL for women. Using a Cox Proportional Hazards model, we estimated the hazard ratio (HR) and confidence intervals (CI) of incident gout by baseline anemia, adjusted for confounders (sex, race, estimated glomerular filtration rate, body mass index and alcohol intake) and clinical factors (coronary heart disease, congestive heart failure, diabetes, hypertension, diuretic use and serum urate level). RESULTS:Among the 10,791 participants, 10% had anemia at baseline. There were 271 cases of incident gout. Patients with anemia had a two-fold increased risk of developing gout over nine years (HR = 2.01, 95% CI: 1.46, 2.76). Anemia was associated with incident gout independent of known gout risk factors, confounders and clinical risk factors (HR = 1.73, 95% CI: 1.24, 2.41). This association persisted after additionally adjusting for serum urate level (HR = 1.83, 95% CI: 1.30, 2.57). CONCLUSION/CONCLUSIONS:We identified anemia as a novel risk factor for gout. Anemia was associated with an approximately two-fold increased risk of gout-independent kidney function and serum urate. These findings suggest that anemia is a risk factor for gout on par with other chronic conditions such as obesity and diabetes. The biological mechanism linking anemia to gout remains unclear.

BACKGROUND:We hypothesized that women with early- and mid-adult life obesity, as well as high mid-adult life waist-to-hip ratios, and high weight gain during adulthood, experience a greater incidence of gout. METHODS:We examined the incidence of gout in the Atherosclerosis Risk in Communities Study, a population-based biracial cohort comprised of individuals aged 45-65 years at baseline (1987-1989). A total of 6263 women without prior history of gout were identified. We examined the association of body mass index (BMI) and obesity at cohort entry and at age 25 years, waist-to-hip ratio, and weight change with gout incidence (1996-1998). RESULTS:Over 9 years of follow-up, 106 women developed gout. The cumulative incidence of gout, by age 70 years, according to BMI category at baseline of <25, 25-29.9, 30-34.9, and ≥35 kg/m(2), was 1.9, 3.6, 7.9, and 11.8%, respectively (P <.001). Obese women (BMI ≥30) at baseline had an adjusted 2.4-fold greater risk of developing gout than nonobese women (95% confidence interval [CI], 1.53-3.68). This association was attenuated after further adjustment for urate levels. Further, early adult obesity in women was associated with a 2.8-fold increased risk of gout compared with nonobese women (95% CI, 1.33-6.09), which remained statistically significant after baseline urate adjustment. There was a graded association between each anthropometric measure, including weight gain, with incident gout (each P for trend <.001). The results were similar in black and white women. CONCLUSIONS:In a large cohort of black and white women, obesity in early- and mid-adulthood, and weight gain during this interval, were each independent risk factors for incident gout in women.

OBJECTIVE:To quantify the role of diuretic use in gout development in an adult population with hypertension. METHODS:The Atherosclerosis Risk in Communities study, a prospective population-based cohort from 4 US communities, consisted of 4 visits over a 9-year period. Participants were included in this analysis if they answered a query about gout, were free of gout at baseline, and had hypertension (defined as taking medication to treat hypertension or having blood pressure of ≥140/90 mm Hg). Trained interviewers recorded use of antihypertensive drugs. Incident gout was defined as self-reported onset of gout after baseline. Using a time-dependent Cox proportional hazards model, we estimated hazard ratios (HRs; with 95% confidence intervals [95% CIs]) for incident gout by time-varying diuretic use, both adjusted for confounders and tested for mediation by serum urate level. RESULTS:There were 5,789 participants with hypertension; 37% were treated with a diuretic. Use of any diuretic (HR 1.48 [95% CI 1.11, 1.98]), a thiazide diuretic (HR 1.44 [95% CI 1.00, 2.10]), or a loop diuretic (HR 2.31 [95% CI 1.36, 3.91]) was associated with incident gout as compared with not using any diuretic, not using a thiazide diuretic, or not using a loop diuretic, respectively. After adjusting for serum urate level, the association between diuretic use and gout was null. Use of antihypertensive medication other than diuretic agents was associated with decreased gout risk (adjusted HR 0.64 [95% CI 0.49, 0.86]) compared to untreated hypertension. The longitudinal change in serum urate levels was 0.72 mg/dl (95% CI 0.57, 0.87) higher in those who began treatment with a diuretic than in those who did not (P<0.001). CONCLUSION/CONCLUSIONS:Thiazide and loop diuretics were associated with increased gout risk, an association mediated by a change in serum urate levels.

Hypertension status among spouses is known to be concordant, but previous studies relied on history rather than direct measurement, and few data exist on treatment and control between spouses. The goal of this study was to estimate the spousal association of hypertension status, treatment, and control in adults. The authors identified and analyzed data on 4,500 pairs from the Atherosclerosis Risk in Communities (ARIC) cohort, which sampled middle-aged adults and their spouses in 1986-1989, with 3 follow-up visits 3 years apart. Generalized estimating equations were used in logistic regression analyses to calculate the odds ratio of a spouse's being hypertensive on the basis of the other spouse's hypertension status across 4 visits, adjusting for age, race, body mass index, smoking status, and sodium intake in both individuals. There are marginally increased odds of hypertension for spouses married to someone with hypertension (odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.06, 1.25). Treatment was positively associated between spouses (OR = 1.35, 95% CI: 1.10, 1.67). Control was suggestive of an association, although it was not statistically significant (OR = 1.21, 95% CI: 0.93, 1.56). In middle-aged adults, hypertension status and treatment were moderately associated between spouses after controlling for shared environment. Physicians may target hypertension education and prevention to spouses as a pair rather than as 2 separate patients.