Heart Disease Can Be Prevalent in Men With ATTRv Amyloidosis

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by Patricia Inacio PhD |

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Heart involvement is more prevalent among men with hereditary transthyretin (ATTRv) amyloidosis, a group of rare disorders that includes familial amyloid polyneuropathy (FAP), a study reports.

Findings suggest that female sex may be protective against heart disease in ATTRv, and that being male may also contribute to disease worsening.

The study, “Sex-Related Risk of Cardiac Involvement in Hereditary Transthyretin Amyloidosis: Insights From THAOS,” was published in the Journal of the American College of Cardiology: Heart Failure.

ATTRv amyloidosis is a disease caused by a faulty form of the protein transthyretin, which clumps together and forms abnormal deposits in different tissues and organs, including the heart, disrupting its function. FAP is a specific form of ATTRv amyloidosis in which transthyretin aggregates, also known as amyloid deposits, mainly accumulate in nerves, resulting in nerve damage.

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The accumulation of amyloid deposits in the heart leads to a condition called cardiomyopathy, a disease in which the heart muscle loses its ability to pump blood effectively.

Previous studies suggest that cardiomyopathy is more likely in men with ATTRv amyloidosis, but sex differences with this disease have only occasionally been reported, the study noted.

A team of researchers in Italy and their colleagues evaluated the prevalence of heart involvement and its risk factors, particularly the role of sex, in a group of patients with ATTRv amyloidosis.

They analyzed data from people enrolled in the observational Transthyretin Amyloidosis Outcomes Survey (THAOS) study. THAOS (NCT00628745) is the largest global registry of patients with ATTR amyloidosis.

Data analyzed covered 2,790 patients with ATTRv amyloidosis  (1,646 men and 1,144 women). Men were older than women at enrollment (mean age of 54.2 vs. 50.4).

More men showed signs of heart involvement compared with women, as shown by tests measuring heart wall thickness and the left ventricular ejection fraction (LVEF), which measures how much blood is being pumped out of the heart’s left ventricle (the main pumping chamber) with each contraction.

Cardiac symptoms were more common in men than women (18% vs. 13%); the reverse was seen with neurological symptoms (57.4% in men vs. 64.6% in women).

Men represented the highest proportion of patients (683 in total) with hereditary ATTRv amyloidosis and cardiomyopathy — defined as a left ventricle wall thickness greater than 12 mm — compared with women (72.2% vs. 27.8%).

Male patients also had significantly more severe symptoms and worse heart disease progression, as shown in multiple measures.

Further statistical analyses found that sex, age at disease onset, and genetic background were risks factors associated with a greater thickness of the left ventricular septum — a parameter indicative of heart disease. However, sex alone was not confirmed as an independent risk factor for the development of cardiomyopathy.

Researchers then analyzed data from 4,050 patients (2,171 men and 1,879 women) carrying a disease-causing mutation in the TTR gene, which provides instructions for making transthyretin. Of this group, 2,790 developed ATTRv amyloidosis, and 1,646 of them (59%) were men.

The most common mutation found in the TTR gene was Val30Met and its frequency was higher in women compared with men (72%vs. 60.2%). In contrast, other non-Val30Met heart mutations — including Val122Ile, Leu111Met, Thr60Ala, or Ile68Leu — were more common in male patients, especially those with ATTRv amyloidosis.

Male prevalence was also higher among patients with hereditary ATTRv amyloidosis and cardiomyopathy, regardless of mutations. Among these Val30Met patients, male prevalence was even more pronounced.

“This large analysis in THAOS suggests that [heart] involvement appears to be more frequent and pronounced in male patients with ATTRv amyloidosis,” the researchers wrote.

“Future studies might investigate potential prognostic factors and examine the underlying biology of a potential protective mechanism conferred by female sex,” they added.