Phenoage and longitudinal changes on transthoracic echocardiography in Alström syndrome: a disease of accelerated ageing?

• Published in: GeroScience Vol. 46; no. 2; pp. 1989 - 1999
• Main Authors: Patel, Leena, Roy, Ashwin, Alvior, Amor Mia B, Yuan, Mengshi, Baig, Shanat, Bunting, Karina V., Hodson, James, Gehmlich, Katja, Lord, Janet M, Geberhiwot, Tarekegn, Steeds, Richard P.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2024; Springer Nature B.V
• Subjects: Aged; Aging; Alstrom Syndrome - diagnostic imaging; Alstrom's syndrome; Biomedical and Life Sciences; Cardiovascular diseases; Cell Biology; Cross-Sectional Studies; Diastole; Dyslipidemia; Echocardiography; Female; Geriatrics/Gerontology; Heart; Humans; Insulin resistance; Life Sciences; Male; Molecular Medicine; Original; Original Article; Retrospective Studies; Ventricle; Ventricular Dysfunction, Left; Phenoage; Rare diseases; Echocardiography; Cardiovascular; Ageing
• ISSN: 2509-2723; 2509-2715; 2509-2723
• DOI: 10.1007/s11357-023-00959-3

Alström syndrome (AS) is an ultra-rare disorder characterised by early-onset multi-organ dysfunction, such as insulin resistance, obesity, dyslipidaemia, and renal and cardiovascular disease. The objective is to explore whether AS is a disease of accelerated ageing and whether changes over time on echocardiography could reflect accelerated cardiac ageing. Cross-sectional measurement of Phenoage and retrospective analysis of serial echocardiography were performed between March 2012 and November 2022. The setting is a single national tertiary service jointly run by health service and patient charity. Forty-five adult patients aged over 16 years were included, 64% were male and 67% of White ethnicity. The median Phenoage was 48 years (interquartile range [IQR]: 35–72) in the 34 patients for whom this was calculable, which was significantly higher than the median chronological age of 29 years (IQR: 22–39, p <0.001). Phenoage was higher than chronological age in 85% ( N =29) of patients, with a median difference of +18 years (IQR: +4, +34). On echocardiography, significant decreases were observed over time in left ventricular (LV) size at end-diastole (average of 0.046 cm per year, p <0.001) and end-systole (1.1% per year, p =0.025), with significant increase in posterior wall thickness at end-diastole (0.009 cm per year, p =0.008). LV systolic function measured by global longitudinal strain reduced (0.34 percentage points per year, p =0.020) and E/e’lat increased (2.5% per year, p =0.019). Most AS patients display a higher Phenoage compared to chronological age. Cardiac changes in AS patients were also reflective of accelerated ageing, with a reduction in LV size and increased wall thickening. AS may be a paradigm disease for premature ageing.