U-shaped relationship between tissue docosahexaenoic acid and atrial fibrillation following cardiac surgery.

BACKGROUND/OBJECTIVES: Randomised controlled trials (RCTs) evaluating the effect of fish oil supplementation on postoperative atrial fibrillation (POAF) following cardiac surgery have produced mixed results. In this study, we examined relationships between levels of red blood cell (RBC) n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) and the incidence of POAF. SUBJECTS/METHODS: We used combined data (n=355) from RCTs conducted in Australia and Iceland. The primary end point was defined as POAF lasting >10 min in the first 6 days following surgery. The odds ratios (ORs) for POAF were compared between quintiles of preoperative RBC n-3 LC-PUFA levels by multivariable logistic regression. RESULTS: Subjects with RBC docosahexaenoic acid (DHA) in the fourth quintile, comprising a RBC DHA range of 7.0-7.9%, had the lowest incidence of POAF. Subjects in the lowest and highest quintiles had significantly higher risk of developing POAF compared with those in the fourth quintile (OR=2.36: 95% CI; 1.07-5.24 and OR=2.45: 95% CI; 1.16-5.17, respectively). There was no association between RBC eicosapentaenoic acid levels and POAF incidence. CONCLUSIONS: The results suggest a 'U-shaped' relationship between RBC DHA levels and POAF incidence. The possibility of increased risk of POAF at high levels of DHA suggests an upper limit for n-3 LC-PUFAs in certain conditions.

Inflammatory response following heart surgery and association with n-3 and n-6 long-chain polyunsaturated fatty acids in plasma and red blood cell membrane lipids.

BACKGROUND: Open heart surgery is associated with a systemic inflammatory response. The n-3 long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the n-6 LC-PUFA arachidonic acid (AA) may contribute to modulation of the inflammatory response. OBJECTIVE: We investigated whether the preoperative levels of EPA, DHA and AA in plasma phospholipids (PL) and red blood cell (RBC) membrane lipids in patients (n=168) undergoing open heart surgery were associated with changes in the plasma concentration of selected inflammatory mediators in the immediate postoperative period. RESULTS AND CONCLUSIONS: The postoperative concentration of TNF-ß was lower (P<0.05) and those of hs-CRP, IL-6, IL-8, IL-18 and IL-10 higher (P<0.05) than the respective preoperative concentrations. We observed that the preoperative levels of EPA and AA in plasma PL and RBC membrane lipids were associated with changes in the concentration of pro-inflammatory and anti-inflammatory mediators, suggesting a complex role in the postoperative inflammatory process.

Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Durham Renal Osteodystrophy Study Group.

UNLABELLED: Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. BACKGROUND: In the management of patients with mild secondary hyperparathyroidism, it is not known whether calcium supplementation alone is sufficient to correct abnormalities in bone and mineral metabolism or if calcitriol is needed in either physiologic oral or intravenous pharmacologic doses. METHODS: This was a 40-week prospective nonmasked trial of 52 patients [parathyroid hormone (PTH) 150 to 600 pg/mL] who were randomized to receive escalating doses of either calcium carbonate (CaCO3) alone (calcium group, N = 11), daily oral calcitriol (oral group, N = 20), or intermittent intravenous calcitriol (IV group, N = 21). The groups were compared with regard to changes in serum intact PTH, serum bone-specific alkaline phosphatase (BAP), incidence of hypercalcemia (>10.5 mg/dL), and hyperphosphatemia (>6.5 mg/dL). RESULTS: PTH levels decreased in all groups (P < 0.01, paired t-test). In the calcium group, PTH (mean +/- SEM) decreased from 325 +/- 46.2 to 160 +/- 44.5 pg/mL. In the oral group, it decreased from 265 +/- 26.4 to 125 +/- 23.7 pg/mL, and in the IV group, it decreased from 240 +/- 27.7 to 65 +/- 10.0 pg/mL. Upon analysis of covariance, controlling for the initial PTH level, we found no differences in the PTH response between the groups (P > 0.10). In contrast, the BAP concentration increased from 20.7 +/- 7.6 to 27.5 +/- 7.0 microg/L in the calcium group (P = 0.17), decreased from 20. 6 +/- 3.9 to 17.8 +/- 4.5 microg/L in the oral group (P = 0.26), and from 19.1 +/- 2.6 to 10.6 +/- 1.1 microg/L in the IV group (P = 0. 007). Serum calcium increased significantly in all groups from 8.4 +/- 0.25 to 9.0 +/- 0.28, 8.5 +/- 0.16 to 9.2 +/- 0.27, and 8.7 +/- 0.16 to 9.4 +/- 0.18 mg/dL in the calcium, oral, and IV groups, respectively (P = NS difference between groups). Serum phosphorus was significantly lower in the calcium group throughout the study (P = 0.02). Hypercalcemic episodes were 2.0 +/- 0.8, 3.0 +/- 0.6, and 3. 4 +/- 0.6 per patient-year (P > 0.10), and hyperphosphatemic episodes were 0.9 +/- 0.56, 4.2 +/- 0.79 and 4.9 +/- 0.84 in the calcium, oral, and IV groups, respectively (P < 0.01). CONCLUSION: In mild secondary hyperparathyroidism, all three strategies are effective. High-dose CaCO3 alone may be sufficient to control PTH with a favorable side-effect profile, but calcitriol appears to have additional suppressive effects on bone that are greater following the intravenous route of administration and may increase the risk of adynamic bone disease.

Predictors of short-term changes in serum intact parathyroid hormone levels in hemodialysis patients: role of phosphorus, calcium, and gender.

Several factors have been identified as important in the pathogenesis of secondary hyperparathyroidism in end-stage renal disease, including serum calcium, phosphorus, and calcitriol. To examine the independent effects of key factors, we prospectively studied 52 new hemodialysis patients with mild secondary hyperparathyroidism (PTH, 110-670 pg/mL) treated with a standardized regimen of calcium supplements, phosphorus binders, and no vitamin D derivatives. We used simple and multivariable linear regression analysis to examine the relationship between changes in PTH (deltaPTH) levels observed over a 4-week period and various biochemical and demographic variables. By simple linear regression we found that changes in serum phosphorus (r2 = 0.31; beta = 41.6; P = 0.0001), initial phosphorus concentration (r2 = 0.15; beta = 33.4; P = 0.005), initial PTH level (r2 = 0.29; beta = 0.58; P = 0.0001), changes in serum calcium (r2 = 0.12; beta = -74.0; P = 0.01), and gender (r2 = 0.07; beta = 76.1; P = 0.05) were significantly associated with deltaPTH. However, upon multivariable regression analysis, only the changes in phosphorus (partial r2 = 0.31; beta = 37.0; P = 0.0001), initial PTH level (partial r2 = 0.23; beta = 0.50; P = 0.0001), and gender (partial r2 = 0.05; beta = 63.1; P = 0.02) remained significantly associated with deltaPTH. Neither the serum concentration of 1,25-dihydroxyvitamin D3, bicarbonate, aluminum, or albumin nor changes in the serum bicarbonate concentration, the presence of diabetes, KT/V, or age were significantly associated with the deltaPTH. Our findings are consistent with independent effects of phosphorus and gender on parathyroid gland function in patients with dialysis-dependent renal failure through mechanisms that remain to be defined.