Letter by Reeder and Anderson Regarding Article, “Heart Failure is a Risk Factor for Orthopedic Fracture: A Population-Based Analysis of 16 294 Patients”
Results from the trial by van Diepen and colleagues1 found a statistically significant association between the diagnosis of heart failure (HF) and risk of orthopedic fracture in a large cohort of elderly patients with known cardiovascular disease. Although a pathophysiological link between HF and osteoporosis remains to be determined, the authors offer a potential cause beyond that of shared risk factors. The backbone of the proposed mechanism in HF is elevated aldosterone levels, which have been associated with increased urinary calcium and magnesium excretion, hyperparathyroidism, and diminished bone mineral density. One relationship that also deserves recognition is the association between HF, hyponatremia, and increased risk of falls and fractures.
Hyponatremia in HF is relatively common with a prevalence of 20% in a large registry of over 48 000 HF patients.2 Hyponatremia may reveal a more pronounced activation of the renin-angiotensin-aldosterone system, sympathetic nervous system, and vasopressin release.3 Therefore, hyponatremia may identify a population with a pathophysiological profile that differs from that of eunatremic HF patients. This population may be at an increased risk of falls and fractures.
Hyponatremia has been associated with an increase in the risk of falls. In one case-control study of asymptomatic chronic hyponatremic patients, hyponatremia was associated with a higher incidence of falls, possibly as a result of gait and attention deficits.4 Furthermore, the frequency of falls was the same regardless of level of hyponatremia, highlighting the observation that even mild hyponatremia (serum Na+, 130 to 132 mmol/L) is linked to an increase in falls.
In addition to evidence that illustrates an increased risk of falls, hyponatremia has been associated with an increased risk of fractures. One case-control study looked at the relationship between hyponatremia and bone fractures from incidental falls in elderly ambulatory patients.5 In this study, hyponatremia (defined as serum Na+ <135 mmol/L) was associated with a greater than 3-fold increased risk of bone fracture after incidental fall (odds ratio, 3.47; 95% confidence interval, 2.09 to 5.79). The authors suggest that attention deficits and gait instability observed in elderly hyponatremic patients may explain the relationship between hyponatremia and bone fracture. This reaffirms the notion that hyponatremic patients represent a unique population that should not be overlooked, in particular when assessing outcomes that include fractures.
Although the pathogenesis of hyponatremia in HF is usually multifactorial, the use of diuretics is most often implicated. In addition, patients with HF have an overstimulated renin-angiotensin-aldosterone system. Increased angiotensin II stimulates vasopressin release resulting in water resorption through increased production of aquaporin channels, ultimately causing hypervolemic hyponatremia.
The trial by van Diepen and colleagues has provided the HF community with a valuable insight into the association between HF and an increased risk of fracture. It is quite common that many HF patients have hyponatremia that is likely due to increased vasopressin release. In light of this and the presented evidence relative to hyponatremia and an increased risk of both falls and fractures, it would be beneficial to the readership for the authors to further explore the data with consideration of serum sodium levels.
van Diepen S, Majumdar SR, Bakal JA, McAlister FA, Ezekowitz JA. Heart failure is a risk factor for orthopedic fracture: a population-based analysis of 16 294 patients. Circulation. 2008; 118: 1946–1952.
Gheorghiade M, Abraham WT, Albert NM, Gattis Stough W, Greenberg BH, O'Connor CM, She L, Yancy CW, Young J, Fonarow GC; OPTIMIZE-HF Investigators and Coordinators. Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry. Eur Heart J. 2007; 28: 980–988.
Gheorghiade M, Niazi I, Ouyang J, Czerwiec F, Kambayashi J, Zampino M, Orlandi C; Tolvaptan Investigators. Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation. 2003; 107: 2690–2696.
Gankam Kengne F, Andres C, Sattar L, Melot C, Decaux G. Mild hyponatremia and risk of fracture in the ambulatory elderly. QJM. 2008; 101: 583–588.