Troponin I levels elevated in FA patients without cardiac symptoms: Study
Being younger, female, having high GAA repeat count tied to higher protein levels
People with Friedreich’s ataxia (FA) may have elevated blood levels of cardiac troponin I and T, markers of heart damage, without signs of heart dysfunction, a study suggests.
Being younger, female, or having a higher number of GAA repeats, the main type of FA-causing mutation, was associated with higher troponin I in these patients. Troponin I blood levels also were associated with a higher risk of developing irregular heartbeat or other alterations to heart function.
The study, “Characterization of clinical serum cardiac biomarker levels in individuals with Friedreich ataxia,” was published in the Journal of the Neurological Sciences.
FA is caused by mutations in the FXN gene, usually a repeat expansion of a GAA sequence of nucleotides, which are DNA’s building blocks, disrupting the gene’s ability to produce frataxin. Low frataxin impairs the ability of mitochondria, the cell’s powerhouses, to produce energy, causing inflammation and oxidative stress, which is a type of cell damage caused by high levels of a radical oxygen species.
This leads to progressive nerve cell damage. Symptoms include loss of coordination and muscle control, called ataxia, and heart problems, particularly cardiomyopathy, which affects the heart muscle.
The protein troponin can be found in the heart in two forms, I and T. Damage to the heart muscle’s cells causes troponin to leak into the bloodstream.
Elevated troponin levels in FA
Although some people with FA have elevated troponin I in their blood, “the exact relationship of elevated cTnI levels to [disease-related] changes in [FA] is unclear and its relation to the temporal course of cardiomyopathy is unknown,” wrote researchers in the U.S., who characterized blood biomarkers of cardiac damage, particularly troponin I and T, and also B-type natriuretic peptide (BNP) in FA, and evaluated their association with clinical features of the disease in more than 300 participants (mean age, 22.4) who took part in the study.
Most samples resulted from unprovoked troponin measurements, obtained in 299 patients during other FA screening assessments (asymptomatic). A smaller percentage (13.5%), corresponded to patients with cardiac symptoms, such as heart attack, heart failure or abnormal heart rhythm, so were deemed provoked.
Abnormal values of troponin I were found in 36% of unprovoked samples and in 70% of provoked measurements. Also, the values were higher in provoked evaluations (1.53 vs. 0.17 nanograms/mL).
The protein’s mean levels decreased slightly over time in those with multiple troponin I measurements. This could reflect lower troponin levels with older age and longer disease duration, the scientists said.
Younger age, being female, and a longer GAA repeat length predicted high troponin I in unprovoked (asymptomatic) situations, a statistical analysis showed. Results were similar both in the first and the latest samples, which were available for 188 patients.
The T form was elevated in 28% of unprovoked measurements. In contrast, BNP values were mostly in the low normal range and weren’t associated with FA features such as GAA repeat length.
The researchers then analyzed whether echocardiographic measurements could predict abnormal unprovoked troponin I levels. Echocardiography is a cardiac ultrasound that examines the heart structure and blood flow.
Overall, measures of heart hypertrophy, that is, enlargement, could predict elevated troponin I, “suggesting that cardiac hypertrophy is a minor component in the genesis of [troponin I] values,” wrote the researchers, who said females having higher troponin “connects troponin elevation to a [non-disease related] element in [FA] along with a contribution from the level of hypertrophy.”
Although to a modest degree, troponin I levels could predict long-term markers of cardiac dysfunction, including irregular heartbeat, a decline in the heart’s pumping function, or cardiac death.
“Overall, these data suggest that elevated troponin values provide weak, but significant, markers for eventual cardiac dysfunction in [FA],” the scientists said. “Consequently, troponin I values provide a marker of hypertrophy, but only a minimally predictive biomarker for later cardiac manifestations of disease.”
