Chronic hyponatremia and association with osteoporosis among a large racially/ethnically diverse population.

Chronic hyponatremia may contribute to decreased bone density. We studied 341,003 men and women who underwent DXA testing and observed that individuals with chronic hyponatremia (sodium < 135 mEq/L) had an 11% greater likelihood of having osteoporosis. There was a dose-dependent effect with lower sodium and stronger association with osteoporosis. INTRODUCTION: Chronic hyponatremia has been associated with both neurologic deficits and increased risk of gait abnormalities leading to falls and resultant bone fractures. Whether chronic hyponatremia contributes to decreased bone density is uncertain. We evaluated whether chronic, mild hyponatremia based on serial sodium measurements was associated with increased risk of osteoporosis within a large, ethnically diverse population. METHODS: This is a retrospective cohort study between January 1, 1998 and December 31, 2014 within Kaiser Permanente Southern California, an integrated healthcare delivery system. Men and women were aged ≥ 55 years with ≥ 2 serum sodium measurements prior to dual-energy X-ray absorptiometry (DXA) testing. Time-weighted (TW) mean sodium values were calculated by using the proportion of time (weight) elapsed between sodium measurements and defined as < 135 mEq/L. Osteoporosis defined as any T-score value ≤ - 2.5 of lumbar spine, femoral neck, or hip. RESULTS: Among 341,003 individuals with 3,330,903 sodium measurements, 11,539 (3.4%) had chronic hyponatremia and 151,505 (44.4%) had osteoporosis. Chronic hyponatremic individuals had an osteoporosis RR (95% CI) of 1.11 (1.09, 1.13) compared to those with normonatremia. A TW mean sodium increase of 3 mEq/L was associated with a lower risk of osteoporosis [adjusted RR (95% CI) 0.95 (0.93, 0.96)]. A similar association was observed when the arithmetic mean sodium value was used for comparison. CONCLUSIONS: We observed a modest increase in risk for osteoporosis in people with chronic hyponatremia. There was also a graded association between higher TW mean sodium values and lower risk of osteoporosis. Our findings underscore the premise that chronic hyponatremia may lead to adverse physiological effects and responses which deserves better understanding.

Prognostic value of hyponatremia in heart failure patients: an analysis of the Clinical Characteristics and Outcomes in the Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (COAST) study.

BACKGROUND/AIMS: Hyponatremia is a well-known risk factor for poor outcomes in Western studies of heart failure (HF) patients. We evaluated the predictive value of hyponatremia in hospitalized Asian HF patients. METHODS: The Clinical Characteristics and Outcomes in the Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (the COAST) study enrolled hospitalized patients with systolic HF (ejection fraction < 45%) at eight centers in South Korea, Taiwan, and China. The relationship between admission sodium level and clinical outcomes was analyzed in 1,470 patients. RESULTS: The mean admission sodium level was 138 ± 4.7 mmol/L, and 247 patients (16.8%) had hyponatremia defined as Na(+) < 135 mmol/L. The 12-month mortality was higher in hyponatremic patients (27.9% vs. 14.6%, p < 0.001), and hyponatremia was an independent predictor of 12-month mortality (hazard ratio, 1.72; 95% confidence interval, 1.12 to 2.65). During hospital admission, 57% of hyponatremic patients showed improvement without improvement in their clinical outcomes (p = 0.620). The proportion of patients with optimal medical treatment was only 26.5% and 44.2% at admission and discharge, respectively, defined as the combined use of angiotensin-converting-enzyme inhibitor/angiotensin receptor blocker and ß-blocker. Underuse of optimal medical treatment was more pronounced in hyponatremic patients. CONCLUSIONS: In hospitalized Asian HF patients, hyponatremia at admission is common and is an independent predictor of poor clinical outcome. Furthermore, hyponatremic patients receive less optimal medical treatment than their counterparts.

Mild hyponatremia is associated with an increased risk of death in an ambulatory setting.

Hyponatremia is a common disorder associated with higher mortality in hospitalized patients, but its impact in an ambulatory setting remains unclear. Here we used data from the Dallas Heart Study, a prospective multiethnic cohort study that included ambulatory individuals, to determine the prevalence and determinants of hyponatremia (serum sodium <135 mEq/l), and its impact on mortality. The analysis included 3551 individuals with a median age of 43 years followed up over a median of 8.4 years. The sample weight-adjusted prevalence of hyponatremia was 6.9%. Hyponatremia was mild (median serum sodium: 133 mEq/l), and was significantly associated with age, black ethnicity, presence of cirrhosis or congestive heart failure, and use of selective serotonin reuptake inhibitors. By the end of the follow-up period, there were 202 deaths including 29 in hyponatremic individuals. The unadjusted hazard ratio for hyponatremia and death was 1.94. Hyponatremia remained significantly associated with mortality after adjustment for age, gender, ethnicity, diabetes, hypertension, dyslipidemia, smoking, alcohol use, renal function, plasma C-reactive protein, use of antiepileptic drugs and selective serotonin reuptake inhibitors, and history of congestive heart failure, cirrhosis, and cancer (hazard ratio of 1.75). Thus, mild hyponatremia is associated with an increased risk of death in a young and ethnically diverse community population.

Low serum sodium as a poor prognostic indicator for mortality in congestive heart failure patients.

BACKGROUND: The incidence of congestive heart failure (CHF) has not significantly declined over the past 50 years, and overall survival rates are low at 5 years following diagnosis. Numerous studies have shown low serum sodium to be a poor prognostic indicator of all cause mortality in CHF patients. HYPOTHESIS: The goal of this hypothesis was to validate if hyponatremia is an important predictor of mortality in an outpatient population of CHF patients on maximal combined angiotensin-converting enzyme inhibitor (ACEI) and ß-blocker therapy. METHODS: A total of 364 (13% with hyponatremia) patients with CHF (ejection fraction [EF] ≤ 40%) were enrolled in a heart failure disease management program. The mean New York Heart Association (NYHA) class was II.XII. The average baseline serum sodium was 138.2 mEq/L. RESULTS: We evaluated the relationship between hyponatremia (<135 mEq/L) and all-cause mortality at 40 months. During follow-up, 8 patients in the hyponatremia group compared to 31 in the normonatremic group died. Results of Kaplan-Meier analyses indicated there were no significant differences in mortality between the hyponatremia and normonatremic groups (log-rank test = 0.39). Results for Cox proportional hazards models indicated low sodium was not a significant predictor of mortality (unadjusted odds ratio [OR]: 1.41, 95% confidence interval [CI]: 0.65, 3.07; adjusted OR: 1.60, 95% CI: 0.57, 4.53). CONCLUSIONS: The relationship between hyponatremia and all-cause mortality did not reach significance. Hyponatremia did not significantly predict mortality in a CHF population on maximal medical therapy. Copyright © 2010 Wiley Periodicals, Inc.

Hyponatremia and syndrome of inappropriate anti-diuretic hormone reported with the use of Vincristine: an over-representation of Asians?

PURPOSE: This retrospective study used a pharmaceutical company's global safety database to determine the reporting rate of hyponatremia and/or syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) among vincristine-treated patients and to explore the possibility of at-risk population subgroups. METHOD: We searched the Eli Lilly and Company's computerized adverse event database for all reported cases of hyponatremia and/or SIADH as of 1 November 1999 that had been reported during the use of vincristine. RESULTS: A total of 76 cases of hyponatremia and/or SIADH associated with vincristine use were identified. The overall reporting rate was estimated to be 1.3/100,000 treated patients. The average age of patients was 35.6 +/- 28.3 years, and 62% were males. Approximately 75% of the patients were receiving treatment for leukemia or lymphoma. Among the 39 reports that included information on race, the racial distribution was: 1 Black, 3 Caucasian, and 35 Asian. CONCLUSION: Our data suggest that Asian patients may be at increased risk of hyponatremia and/or SIADH associated with vincristine use. Although the overall reported rate of SIADH associated with vincristine is very low, physicians caring for Asian oncology patients should be aware of this potential serious but reversible adverse event.