Columbia researchers have found a link between a common back ailment and a type of heart failure, suggesting that screening patients with lumbar spinal stenosis could identify those at risk of the heart disease and prevent premature deaths.
Once considered rare, the heart disease, called transthyretin amyloid cardiomyopathy, is now thought to be a more common but underdiagnosed cause of heart failure. The disease is caused by proteins called transthyretin that can clump together and create amyloid deposits in the heart, the spine, ligaments, and other tissues. In the heart, the deposits stiffen the walls and reduce the amount of blood the heart can pump.
Until recently, no treatment was available for this type of heart failure. But in 2019, after a clinical trial led by Columbia cardiologist Mathew S. Maurer, MD, the FDA approved a drug that prevents transthyretin amyloid deposition. (Amyloid deposits also appear in Alzheimer’s disease, but those develop from a different protein and cannot be treated with the drug).
“We have a good treatment that reduces the risk of dying from this condition, and now we clearly need a better way to screen people and find those at risk,” says Maurer, professor of medicine at Columbia University Vagelos College of Physicians and Surgeons. “Because the drug does not reduce existing amyloid, it’s most effective when taken early in the disease.”
Screening back patients
Recent studies suggest that many patients diagnosed with lumbar spinal stenosis develop transthyretin amyloid cardiomyopathy five to 15 years after their stenosis diagnosis. That led Maurer to consider whether screening stenosis patients who undergo surgery could identify those at risk of transthyretin cardiomyopathy or who are already in the early stages.
“Many spinal stenosis patients undergo spinal surgery, and it is easy to take a sample of tissue removed during the procedure and test it for transthyretin amyloid,” Maurer says. If amyloid is present in the spine, doctors could use advanced imaging or a heart muscle biopsy to determine if the heart is also affected.
To see if such screening would be worthwhile, Maurer’s team at Columbia analyzed spinal tissue from 47 patients (ages 62 to 76) undergoing spinal decompression surgery. The researchers detected amyloid in the spine of 34% of patients; two-thirds had transthyretin amyloid, while the amyloid content of the other third could not be identified.
Among those with confirmed transthyretin amyloid (10 patients), one had already developed cardiac amyloidosis and subsequently began treatment with tafamidis. The other nine patients are being closely monitored by their physicians for future heart problems.
“Based on these findings, we would suggest that all patients who undergo surgery for spinal stenosis should be screened for transthyretin amyloid,” says Maurer. “I’d certainly recommend screening if a patient has additional orthopedic issues, such as carpal tunnel syndrome, joint deterioration, or bicep tendon injury, each of which can be caused by transthyretin amyloid. Such patients are especially likely to have transthyretin amyloid and be at risk for heart failure in the future.”
The results from our cross-sectional analyses showed an association between chronic LBP and lifetime myocardial infarction and a borderline association for myocardial infarction in the last two years. Similarly, there was a relationship between chronic LBP and other coronary heart diseases, both at lifetime and in the last two years, when twins were considered part of the total sample. Further analytical steps, which partially or fully controls for genetics and early shared environment, showed an overall pattern of increase in the magnitude of the association between LBP and coronary heart related diseases, although no statistically significant relationship was observed.
The magnitude of the OR for MZ twins (were highest levels of adjustment are achieved) in the prevalence analysis suggests that although this association is no longer significant, we should not assume that genetics and the early shared environment are confounding the association between chronic LBP, myocardial infarction and other coronary heart diseases. Although the cross-sectional nature of our study limits the possibility of identifying causal relationships, the co-twin control design provides some insight, suggesting the possibility that the association is not completely due to genetics and familial factors and that the loss of significance could reflect a decrease of power due to the reduction in sample size when using discordant pairs and the low prevalence of the outcome. This interpretation is based on the magnitude of the OR in the MZ analysis and plausibility of the effects of LBP on other coronary heart diseases (including myocardial infarction), rather than a narrowed inspection of p-values, which is known to be of limited clinical interpretation and problematic .
There are a number of (non-twin) cross-sectional studies that have investigated the relationship between LBP and coronary heart disease. Overall our results are in general agreement, including a study which found an association between chronic spinal pain and the prevalence of coronary heart disease in adults 18 years or older (OR: 1.3, 95%CI: 1.0 to 1.7) . The presence of severe back pain was significantly associated with the prevalence of cardiovascular disease and myocardial infarction in elderly women (OR: 3.0, 95% CI: 2.0 to 4.6) . General chronic musculoskeletal pain is also associated with higher prevalence estimates of cardiovascular disease in people over 65 years (OR: 1.8, 95%CI: 1.45 to 2.30) , and myocardial infarction (OR: 2.47, 95%CI: 1.43 to 4.28) .
Differences in our study compared to previous studies might be due to variations in study design, such as the definition of our exposure, study samples and outcome measures employed. For example, our study focused on chronic LBP of at least 6 months duration whereas others measured chronic back pain in the last 12 months [11, 18] or chronic musculoskeletal pain either on the day of the survey  or in the last month . A feature of our study is the implementation of a co-twin control design, which allowed the evaluation of genetic and shared familial confounding. Whilst our results might have been affected by power and need to be interpreted with a degree of caution, this method to our knowledge has not been implemented in previous cross-sectional studies of chronic LBP and coronary heart related diseases, therefore providing new insights in this field. Future research should consider high-quality longitudinal designs to explore causal paths, along with larger sample sizes, for example, combining twin data from different datasets in order to evaluate a larger number of discordant twins on a global scale. The International Network of Twin Registries may be a potential source in this regard, as it promotes international collaboration for twin research  and its utilisation may provide more precise estimates and solid conclusions on familial confounding, including genetics across societies.
Given the prevalence of coronary heart disease related to chronic LBP, it is important to consider a number of potential mechanisms underlying this possible relationship. Physiologically, an unhealthy lifestyle adopted due to pain can have a considerable impact on a number of co-morbidities, including coronary heart disease. This seems plausible, given the level of disability and subsequent inactivity associated with LBP . Furthermore, general ‘stress’, elevated cortisol levels , sympathetic-parasympathetic imbalances  and the presence of central sensitization (i.e., pro-inflammatory cytokines)  has been found to be associated with cardiovascular disease and musculoskeletal pain . Psychologically, pain can affect mental health status, triggering symptoms of depression and/or anxiety . Whether the physiological and/or psychological dysfunctions that accompany chronic LBP are cause or effect of this condition, cardiovascular diseases are also associated with these mechanisms . Another potential mechanism which may partially explain this relationship is the presence of atherosclerosis (i.e., atheromatous lesions of lumbar arteries) in the abdominal aorta in people with low back pain . Atherosclerosis limits blood supply and nutritional exchange to the lumbar intervertebral discs, promoting the risk of disc degeneration . Moreover, a high BMI accelerates aortic stiffness, and may act as a preceding lesion prior to aortic plaque formation . Clinicians should therefore be encouraged to routinely monitor individuals with a history of LBP and support them in adopting healthier lifestyle choices .
A major strength of our study, in particular, was a discordant co-twin control analysis on a population-based sample of twins. However, whilst discordant MZ twin pairs allow genetics and the early shared environment to be controlled for, there is the possibility of bias through ‘non-measured’ or ‘non-shared’ variables that differ between members of a MZ pair, which may act as residual confounders, for example occupation exposure. Despite our sample data being obtained via rigorous interviews, the quality of self-reported chronic LBP, myocardial infarction and other coronary heart diseases was based on health-related questionnaires, which could be interpreted differently by different responders, and this may be seen as a limitation, despite the moderate to good agreement between self-report and medical record data for myocardial infarction . There may have also been participants with chronic LBP excluded as they were not diagnosed with coronary heart-related disease by a medical doctor but may have subclinical coronary heart disease (i.e., the presence of some but not all criteria to achieve a diagnosis), such as a family history of cardiovascular disease .
The screening questionnaire provided no information on the severity or duration of chronic LBP, only addressing a single time point, hence it is not known whether people with a history of chronic LBP either recovered, had intermittent or continuous symptoms. In addition, participants may have experienced an episode of LBP during their lifetime and may be subjected to ‘recall bias’, particularly if the pain experience occurred some time ago. However, there is a recurrent, fluctuating course associated with LBP  i.e., acute-on-chronic episodes, which frequently affects a high percentage of individuals in the working population over a long period . Furthermore, additional analysis showed that the prevalence of chronic LBP in our study was similar to the prevalence of LBP reported in the last 2 years—in the same cohort (e.g. lifetime myocardial infarction: 44.7% vs. 42.1%, lifetime coronary heart disease: 48.7% vs. 43.9%). More comprehensive measures in the future may assist, for example, not only for LBP but also in the identification of risk factors for the future onset (or transition to) chronic widespread pain among chronic LBP patients . Prevalence of coronary heart disease may also be due to residual confounding, with chronic pain patients frequently experiencing unmeasured confounders such as symptoms of anxiety or depression –the latter strongly associated with cardiovascular disease . Moreover, our study did not account for hypertension, lipid levels and medication use such as non-steroidal anti-inflammatory drugs, which may increase risk of cardiovascular disease .
reference link :https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865187/
More information: Mathew S. Maurer et al, Analysis of lumbar spine stenosis specimens for identification of amyloid, Journal of the American Geriatrics Society (2022). DOI: 10.1111/jgs.17976