Lifetime physical and athletic activity as novel risk factors in the development of wild-type transthyretin amyloid cardiomyopathy - a prospective multicenter cohort study
N Schwegel, M Ungericht, C Hegen, F Fugger, F Carlozzo, V Santner, V Hoeller, E Kolesnik, K Ablasser, A Zirlik, D Niederseer, P Rainer, C Schmied, G Poelzl, N VerheyenAbstract
Background
Transthyretin amyloidosis (ATTR) is the most common cause of cardiac amyloidosis. Wild-type ATTR, which is associated with ageing, is the most frequent form of amyloidosis. Other than male gender and advanced age, risk factors and underlying pathways for the development of wild-type ATTR cardiomyopathy (wtATTR-CM) are largely unknown. There is rising empirical observation that patients with wtATTR-CM frequently report a substantial history of athletic activity, which might contribute to the manifestation of this disease. However, there is little to no information regarding this relation.
Purpose
To verify strenuous lifetime physical and athletic activity as specific hallmarks of wtATTR-CM.
Methods
This is a prespecified, prospective multicenter cohort study, conducted at two Austrian referral centers for cardiac amyloidosis. The cohort comprises three gender-matched subgroups of (I) patients with wtATTR-CM, (II) patients with heart failure (HF) of other origin, and (III) controls without cardiac disease. All participants underwent a systematic interviewer-administered questionnaire developed in collaboration with sport cardiologists to assess parameters for lifetime physical activity (LPA) and athletic activity (LAA) between their 20th and 60th year of life. LPA was defined as overall activity, including LAA, occupation, and housework. Data was reported in metabolic equivalent of task (MET)-minutes, with estimated MET values per specific activity and intensity according to the Compendium of Physical Activities.
Results
A total of 180 participants were enrolled, comprising 60 participants with wtATTR-CM, HF, and healthy controls each. Median (interquartile range) age in the subgroups was 81 (77-84), 79 (75-84), and 76 (72-80) years, respectively. Patients with wtATTR-CM had a significantly higher LPA (28.3 [20.9-36.2] x10^6 MET-minutes) and LAA (4.6 [1.8-8.2] x10^6 MET-minutes) compared to patients with HF (LPA 17.0 [11.9-20.1] x10^6 MET-minutes, p<0.001; LAA 1.5 [1.0-3.8] x10^6 MET-minutes, p<0.001) and to healthy controls (LPA 18.4 [13.6-23.9] x10^6 MET-minutes, p<0.001; LAA 2.1 [0.9-4.5] x10^6 MET-minutes, p=0.001. Established cardiovascular risk factors, such as arterial hypertension, dyslipidaemia, and smoking, were less prevalent in wtATTR-CM compared to HF and equally prevalent compared to the healthy controls, as displayed in detail in the Table.
Conclusion
In this prospective prespecified multicenter study, patients with wtATTR-CM were characterized by higher activity. Traditional risk factors were less prevalent compared to HF of other origin and similarly prevalent compared to healthy controls. These data suggest that increased activity may be a risk factor for the development of wtATTR-CM. Further prospective studies and mechanistic studies are warranted to elucidate the association between activity and the pathogenesis of wtATTR-CM.Table. Baseline characteristics.For image description, please refer to the figure legend and surrounding text.