Description: Background: We investigated adverse outcomes for people with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) and the effect of comorbidities and demographic factors on these outcomes. Methods: Using linked data (RHD register, hospital, and mortality data) for residents of the Northern Territory of Australia, we calculated ARF recurrence rates, rates of progression from ARF to RHD to severe RHD, RHD complication rates (heart failure, endocarditis, stroke, and atrial fibrillation), and mortality rates for 572 individuals diagnosed with ARF and 1248 with RHD in 1997 to 2013 (94.9% Indigenous). Results: ARF recurrence was highest (incidence, 3.7 per 100 person-years) in the first year after the initial ARF episode, but low-level risk persisted for 〉10 years. Progression to RHD was also highest (incidence, 35.9) in the first year, almost 10 times higher than ARF recurrence. The median age at RHD diagnosis in Indigenous people was young, especially among males (17 years). The development of complications was highest in the first year after RHD diagnosis: heart failure incidence rate per 100 person-years, 9.09; atrial fibrillation, 4.70; endocarditis, 1.00; and stroke, 0.58. Mortality was higher among Indigenous than non-Indigenous RHD patients (hazard ratio, 6.55; 95% confidence interval, 2.45–17.51), of which 28% was explained by comorbid renal failure and hazardous alcohol use. RHD complications and mortality rates were higher for urban than for remote residents. Conclusions: This study provides important new prognostic information for ARF/RHD. The residual Indigenous survival disparity in RHD patients, which persisted after accounting for comorbidities, suggests that other factors contribute to mortality, warranting further research.

Description: Background— Although acute rheumatic fever (ARF) and its sequel, rheumatic heart disease (RHD), continue to cause a large burden of morbidity and mortality in disadvantaged populations, most studies investigating the effectiveness of control programs date from the 1950s. A control program, including a disease register, in the Northern Territory of Australia where the Indigenous population has high rates of ARF and RHD allowed us to examine current disease incidence and progression. Methods and Results— ARF and RHD incidence rates, ARF recurrence rates, progression rates from ARF to RHD to heart failure, and RHD survival and mortality rates were calculated for Northern Territory residents from 1997 to 2010. For Indigenous people, ARF incidence was highest in the 5- to 14-year age group (males, 162 per 100 000; females, 228 per 100 000). There was little evidence that the incidence of ARF or RHD had declined. The ARF recurrence rate declined by 9% per year after diagnosis. After a first ARF diagnosis, 61% developed RHD within 10 years. After RHD diagnosis, 27% developed heart failure within 5 years. For Indigenous RHD patients, the relative survival rate was 88.4% at 10 years after diagnosis and the standardized mortality ratio was 1.56 (95% confidence interval, 1.23–1.96). Conclusions— For Indigenous Australians in the Northern Territory, ARF and RHD incidence and associated mortality remain very high. The reduction in ARF recurrence indicates that the RHD control program has improved secondary prophylaxis; a decline in RHD incidence is expected to follow.

Description: Background Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease resulting from intermittent hypoxia (IH)-induced inflammation. Cyclooxygenase (COX)-formed prostanoids mediate the inflammatory response, and regulate blood pressure and cerebral blood flow (CBF), but their role in blood pressure and CBF responses to IH is unknown. Therefore, this study's objective was to determine the role of prostanoids in cardiovascular and cerebrovascular responses to IH. Methods and Results Twelve healthy, male participants underwent three, 6-hour IH exposures. For 4 days before each IH exposure, participants ingested a placebo, indomethacin (nonselective COX inhibitor), or Celebrex ® (selective COX-2 inhibitor) in a double-blind, randomized, crossover study design. Pre- and post-IH blood pressure, CBF, and urinary prostanoids were assessed. Additionally, blood pressure and urinary prostanoids were assessed in newly diagnosed, untreated OSA patients (n=33). Nonselective COX inhibition increased pre-IH blood pressure ( P ≤0.04) and decreased pre-IH CBF ( P =0.04) while neither physiological variable was affected by COX-2 inhibition ( P ≥0.90). Post-IH, MAP was elevated ( P ≤0.05) and CBF was unchanged with placebo and nonselective COX inhibition. Selective COX-2 inhibition abrogated the IH-induced MAP increase ( P =0.19), but resulted in lower post-IH CBF ( P =0.01). Prostanoids were unaffected by IH, except prostaglandin E 2 was elevated with the placebo ( P =0.02). Finally, OSA patients had elevated blood pressure ( P ≤0.4) and COX-1 formed thromboxane A 2 concentrations ( P =0.02). Conclusions COX-2 and COX-1 have divergent roles in modulating vascular responses to acute and chronic IH. Moreover, COX-1 inhibition may mitigate cardiovascular and cerebrovascular morbidity in OSA. Clinical Trial Registration URL: www.clinicaltrials.gov . Unique identifier: NCT01280006