In this community study, we have shown that newly diagnosed heart failure patients have a higher adjusted prevalence of prior osteoporotic fractures. These patients also experienced a higher adjusted risk of fractures after the heart failure diagnosis, although this association was of borderline statistical significance. Importantly, however, this excess burden of fractures was largely restricted to hip fractures, which both preceded and followed heart failure at significantly higher than expected rates.
Our findings are consistent with a previous study of Swedish women showing that among 1,327 incident hip fracture cases and 3,170 randomly selected population-based controls, the association between cardiovascular disease and hip fracture was more strongly related to heart failure and stroke than to ischemic heart disease.27
Likewise, a recent cohort study of 31,936 Swedish twins demonstrated a substantial increase in hip fracture risk after a diagnosis of heart failure and stroke and underscored the genetic component of the association 25
Furthermore, in a study of 16,294 elderly Canadian patients with cardiovascular disease followed for 1 year, a new diagnosis of heart failure was associated with a 6.3-fold higher risk of developing hip fracture, compared with other cardiovascular disease diagnoses.24
The authors concluded that “heart failure is a risk factor for orthopedic fracture.”24
However, this study relied on administrative data and is thus exposed to misclassification as acknowledged by the authors.24
Our study augments previous reports by examining, in a population-based cohort with rigorous ascertainment of exposure and outcomes, whether there is a higher prevalence of osteoporotic fractures both before and after the diagnosis of heart failure, suggesting a common underlying pathway for both disorders.
The actual basis for the association of heart failure with fracture is unclear. Although traditionally viewed as unrelated disorders of aging, several lines of evidence join both illnesses: 1) reduced BMD and increased bone turnover are associated with increased cardiovascular risk;1-6,7 ,8,9,39
2) cardiovascular risk factors such as vascular calcification, inflammation, and endothelial dysfunction10,11
are associated with low BMD and fractures;12-16
and 3) cardiovascular disease has been associated with an increased risk of falls40,41
and hip fractures,24-27
while others reported increased cardiovascular events in osteoporotic patients.1,3-5
It has also been suggested that the association could reflect shared risk factors, particularly estrogen deficiency, which has been linked to both coronary disease42
although more complex pathophysiological mechanisms may operate.17,18
In addition, traditional cardiovascular risk factors such as dyslipidemia, hypertension, smoking, and diabetes have been reported as associated to osteoporosis.18
None of these mechanistic possibilities could be directly evaluated in the present study. However, if the relationship was mediated through osteoporosis, one would have expected a stronger association with other fractures, especially vertebral fractures, than was seen here. Vertebral fractures, long considered the quintessential osteoporotic fracture,22
were not increased among heart failure patients despite the relatively complete ascertainment of such fractures in this data system.44
The other major factor in fracture etiology is trauma, especially falls. Distal forearm fractures are almost always due to falls, but such falls typically occur when relatively healthy people fall forward onto an outstretched arm.22,45
Forearm fractures were not increased among heart failure patients either. Conversely, falls leading to hip fractures, which were associated with heart failure, occur more often in frail individuals who fall over backwards or to the side and land on the hip.22,46
Given the excess burden of frailty among patients with heart failure,47,48
an important clinical implication of the present data is the need to focus on preventing falls in the heart failure population. Indeed, it was recently pointed out that falling rather than osteoporosis is the strongest single risk factor for fractures in the elderly, a risk that may be reduced by up to 50% by appropriate intervention.49
Some limitations of our study should be acknowledged to aid in data interpretation. As in any observational study, the observed associations could reflect residual confounding due to unmeasured variables or under-ascertainment of measured factors by medical record review. Data on the use of pharmacological treatments possibly related to fracture risk, such as bisphosphonates, corticosteroids, and specific diuretic agents, were not available, and measurements of BMD or biochemical markers of bone turnover were not routinely performed so the role of bone loss in fracture risk could not be examined. Moreover, we could not directly evaluate the many potential pathophysiologic mechanisms that might account for an association between heart failure and hip fracture. Lastly, since the study population was mainly white, these data need replication in other racial and ethnic groups.
The present investigation also has several strengths. We capitalized on the comprehensive data resources of the Rochester Epidemiology Project to examine osteoporotic fractures occurring before and after heart failure. We report on a large, population-based inception cohort registered at the time their heart failure was first confirmed by standardized criteria.32
The controls were randomly selected from an enumeration of the Olmsted County population, and therefore should have been representative of community residents generally.29
Furthermore, the clinical characteristics were recorded prior to any knowledge of resulting fracture outcomes, which were documented in the detailed inpatient and outpatient medical records that spanned each subject's entire period of residency in the community. Finally, fracture ascertainment should be nearly complete since the vast majority come to medical attention either directly or indirectly.44
In conclusion, we found that prior fracture is associated with heart failure at least as strongly as heart failure is associated with subsequent fracture. In both instances, the increased risk is driven by hip fractures rather than other types of fractures. Hip fracture commonly results from falls in frail individuals, suggesting that fracture prevention in elderly patients with heart failure should aim more directly at reducing falls.