Physically demanding jobs linked to higher risk of wild-type ATTR-CM

People with wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) are significantly more likely to have a history of agricultural work, manual labor, and greater upper-body physical strain than the general population, according to a registry-based study in Denmark.

“This included longer durations and higher frequencies of shoulder movements, as well as extended periods of heavy lifting, carrying, pulling, and pushing,” the researchers wrote.

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Still, this study cannot determine whether there is a cause-and-effect relationship between occupational physical exposure and wild-type ATTR-CM, a form of the disease in which age is considered a major risk factor.

Therefore, further studies following people over time are needed to “clarify whether mechanical exposure itself, occupation-specific factors, or unmeasured [influencing factors] explain the observed associations,” the researchers wrote.

The study, “Association Between Occupational Physical Work Exposure and Wild-Type Transthyretin Cardiomyopathy,” was published in JACC: Advances.

ATTR-CM is a form of heart disease in which misfolded transthyretin (TTR) proteins form clumps (amyloid deposits) that build up in the heart muscle. As these deposits accumulate, the heart becomes stiffer and has more difficulty filling and pumping blood, which can lead to heart failure symptoms, abnormal heart rhythms, and reduced survival.

ATTR-CM can be hereditary, caused by mutations in the TTR gene, or wild-type (wt), in which no TTR mutation is present, and age is considered a “major risk factor,” the researchers wrote.

Wild-type ATTR-CM mainly affects older men

wtATTR-CM is diagnosed most often in men, usually after age 60, but exactly why it develops is still not fully understood. Many patients report earlier orthopedic problems or surgeries such as carpal tunnel syndrome (CTS), lumbar spinal stenosis, or hip and knee replacements.

CTS is a condition that affects nerves in the wrist and can cause tingling, pain, and weakness. Lumbar spinal stenosis refers to narrowing of the spinal canal in the lower back, which can cause back or leg pain.

Also, TTR deposits have been found in ligaments and other tissues around joints, “and is believed to be involved in the disease process of these orthopedic lesions,” the researchers wrote.

Data from a previous study showed that a sizable proportion of men with wtATTR-CM have worked in physically demanding jobs, raising questions about whether long-term, repetitive mechanical strain may be linked to the development of TTR amyloid deposits.

To learn more, a team of researchers at Aarhus University Hospital, Denmark analyzed demographic, clinical, and occupational data from people diagnosed with wtATTR-CM between 2016 and 2023.

Researchers compare patients with general population in Denmark

In total, the researchers compared 258 wtATTR-CM patients (median age 82, 91% men) with 1,290 age- and sex-matched people randomly selected from the general Danish population at the time of diagnosis.

While common cardiovascular risk factors, such as high blood pressure and diabetes, were similar between the two groups, people with wtATTR-CM were more likely to have aortic stenosis (15% vs. 5%), a heart condition that restricts blood flow from the heart to the rest of the body.

Atrial fibrillation or flutter, common heart rhythm disorders, were also more prevalent in wtATTR-CM patients (33% vs. 17%), as well as atrioventricular block (6% vs. 2%), a problem with the heart’s electrical signals that can slow the heartbeat.

Accordingly, the wtATTR-CM group was also more likely to be taking heart-related medications.

Several orthopedic problems were also significantly more common in wtATTR-CM patients than in the general population: CTS was about 10.6 times more common, lumbar spinal stenosis and knee arthritis were each more than two times more frequent, and hip arthritis was more than three times more common.

Occupational history also differed. A significantly higher proportion of wtATTR-CM patients — more than three times as many — had worked in agriculture for at least three years compared with the general population (28% vs. 8%). Patients also spent significantly longer working in agriculture on average (11 years vs. seven years).

Orthopedic conditions and heart issues more common in patients

People with wtATTR-CM were also significantly more likely to have a history of manual labor (71% vs. 58%). Detailed occupational data showed significantly greater upper-body physical strain in these patients, including more repetitive shoulder movements, longer periods with arms raised, and more heavy lifting, carrying, pushing, or pulling.

In agreement with previous research, wtATTR-CM was linked to worse survival. Over a median follow-up period of 2.1 years, patients had a 12.1 percentage point higher risk of death at three years compared with matched controls, mainly driven by cardiovascular deaths.

“These results show a potential association between occupational repetitive upper-body mechanical stress and the development of [wtATTR-CM],” the researchers wrote, adding, however, that “the causal [cause-and-effect] relationship cannot be established by the nature of the methodology of study.”