Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in<i>alpha2‐macroglobulin</i>and<i>tau</i>: A population‐based autopsy study

Tanskanen, Maarit; Peuralinna, Terhi; Polvikoski, Tuomo; Notkola, Irma‐Leena; Sulkava, Raimo; Hardy, John; Singleton, Andrew B.; Kiuru-Enari, Sari; Paetau, Anders; Tienari, Pentti J.; Myllykangas, Liisa

doi:10.1080/07853890701842988

Cited by 430 publications

(305 citation statements)

References 33 publications

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“…It is reported that 13% of HFpEF cases were diagnosed as ATTRwt 6. Furthermore, several post‐mortem studies found cardiac amyloid deposition in up to 25% of individuals >80 years of age 7, 8. Therefore, it is important to suspect and differentiate cardiac amyloidosis from HFpEF of other aetiologies for the selection of appropriate therapy and prediction of prognosis.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis

et al. 2017

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AimThe aim of this study was to evaluate the diagnostic utility of high‐sensitivity cardiac troponin T (hs‐cTnT) levels in discriminating cardiac amyloidosis from patients with cardiac hypertrophy caused by aetiologies other than cardiac amyloidosis.Methods and resultsSerum hs‐cTnT levels were measured in 96 patients with cardiac amyloidosis (light chain: 23, wild‐type transthyretin amyloidosis: 40, and mutated transthyretin amyloidosis: 33), and 91 patients with other causes of cardiac hypertrophy who were confirmed to have no cardiac amyloidosis by endomyocardial biopsy (control group). The diagnostic utility and cut‐off value of hs‐cTnT were evaluated by receiver operating characteristic analysis. The median hs‐cTnT levels were higher in cardiac amyloidosis than the control group [0.048 (0.029–0.073) vs. 0.016 (0.010–0.031) ng/mL; P < 0.001]. High levels of hs‐cTnT were suggestive of cardiac amyloidosis (cut‐off value: 0.0312 ng/mL, sensitivity: 0.74, specificity: 0.76, area under the curve: 0.788; 95% confidence interval: 0.723–0.854, P < 0.001), compared with brain natriuretic peptide and E/e′ ratio. The hs‐cTnT levels were also useful in differentiating each type of amyloidosis from the control group. Multivariate analysis identified log hs‐cTnT as an independent diagnostic factor for cardiac amyloidosis (odds ratio: 2.22; 95% confidence interval: 1.30–3.80; P = 0.004).ConclusionsHigh serum levels of hs‐cTnT are highly suggestive of cardiac amyloidosis, allowing its differentiation from cardiac hypertrophy of other aetiologies. Further refined diagnostic approaches that include imaging modalities and histopathological examination are needed for these patients to avoid underdiagnosis of cardiac amyloidosis.

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Section: Introductionmentioning

confidence: 99%

Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis

et al. 2017

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“…An autopsy study on a Finnish population aged 85 or over showed the presence of amyloid deposits in 25%, with a strong correlation between the presence of amyloid and the age at time of death (Tanskanen et al 2008). Amyloid found in heart of the elderly is derived from the transthyretin molecule.…”

Section: Amyloid Depositionmentioning

confidence: 99%

Cardiac aging and heart disease in humans

2017

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The world population continues to grow older rapidly, mostly because of declining fertility and increasing longevity. Since age represents the largest risk factor for cardiovascular disease, the prevalence of these pathologies increases dramatically with increasing age. In order to improve patient care and prevention for age-related cardiac diseases, insight should be gained from the analysis of processes involved in and leading to cardiac aging. It is from this perspective that we provide here an overview of changes associated with age in the heart on four levels: functional, structural, cellular and molecular. We highlight those changes that are in common with the development of the two major age-associated cardiac pathologies: heart failure and atrial fibrillation. These commonly affected processes in aging and cardiac pathophysiology may provide an explanation for the age risk factor in cardiac disease.

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“…5,6 A few post-mortem studies carried out in the United State and European countries reported that the prevalence of senile systemic amyloidosis was 22-25% in patients older than 80 years. [7][8][9] However, the prevalence of senile systemic amyloidosis in other populations, such as those in other Asian countries, remains to be elucidated.…”

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confidence: 99%

Clinicopathological features of senile systemic amyloidosis: an ante- and post-mortem study

et al. 2011

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Senile systemic amyloidosis is a common age-related amyloidosis that involves accumulation of wild-type transthyretin, with cardiac dysfunction being a predominant result. The importance of obtaining an accurate diagnosis of senile systemic amyloidosis has been increasingly recognized, so that novel treatments are being developed. However, the clinicopathological features of senile systemic amyloidosis remain to be completely understood. Here, we evaluated cardiac specimens from 181 consecutive post-mortem cases older than 40 years, including 6 cases of senile systemic amyloidosis, and 5 cases of familial amyloidotic polyneuropathy, which is a hereditary systemic amyloidosis caused by mutant forms of transthyretin. Furthermore, we studied ante-mortem clinicopathological findings of 11 senile systemic amyloidosis cases, in which 9 cases underwent gastrointestinal tract biopsy and/or subcutaneous tissue biopsy, at Kumamoto University Hospital. Of the autopsied cases of elderly Japanese (older than 80 years), 12% had senile systemic amyloidosis, with the percentage increasing with age. The occurrence of senile systemic amyloidosis in elderly Japanese patients was lower than that in previous reports, which suggests that a genetic background and/or environmental factor(s) may have important roles in the occurrence of senile systemic amyloidosis. Transthyretin amyloid deposits in familial amyloidotic polyneuropathy cases developed mainly in the pericardium and the surrounding muscle fascicles, whereas in cases with senile systemic amyloidosis the transthyretin amyloid deposits had a patchy plaque-like shape and developed mainly inside the ventricular wall. Biopsies from senile systemic amyloidosis patients evidenced amyloid deposits in 44% (4/9) of gastrointestinal tract and subcutaneous tissue samples combined. As myocardial biopsy may be dangerous for elderly people, the use of a combination of gastrointestinal tract and subcutaneous tissue biopsies may make diagnosis of senile systemic amyloidosis easier.

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Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation inalpha2‐macroglobulinandtau: A population‐based autopsy study

Abstract: This population-based study shows that SSA is very common in old individuals, affecting one-quarter of people aged over 85 years. Myocardial infarctions and variation in the genes for alpha2M and tau may be associated with SSA.

Cited by 430 publications

References 33 publications

Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis

Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis

Cardiac aging and heart disease in humans

Clinicopathological features of senile systemic amyloidosis: an ante- and post-mortem study

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