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Elevated circulating follistatin associates with increased risk of mortality and cardiometabolic disorders

Pan, Jingxue LU ; Nilsson, Jan LU ; Engström, Gunnar LU and De Marinis, Yang LU (2023) In Nutrition, Metabolism and Cardiovascular Diseases
Abstract

Background and aims: Previous study showed that elevated circulating hepatokine follistatin (FST) associates with an increased risk of type 2 diabetes by inducing adipose tissue insulin resistance. Here we explore further the relationships between plasma FST levels with mortality and health outcomes. Methods and results: The population-based Malmö Diet Cancer cardiovascular cohort (n = 4733, age 45–68 years) was used to study plasma FST in relation to incidence of health outcomes, by linkage with national patient registers. Cox regression analysis was used to assess the associations of plasma FST and outcomes, with adjustments for multiple potential confounding factors. During the mean follow-up time of 22.64 ± 5.84 years in 4,733... (More)

Background and aims: Previous study showed that elevated circulating hepatokine follistatin (FST) associates with an increased risk of type 2 diabetes by inducing adipose tissue insulin resistance. Here we explore further the relationships between plasma FST levels with mortality and health outcomes. Methods and results: The population-based Malmö Diet Cancer cardiovascular cohort (n = 4733, age 45–68 years) was used to study plasma FST in relation to incidence of health outcomes, by linkage with national patient registers. Cox regression analysis was used to assess the associations of plasma FST and outcomes, with adjustments for multiple potential confounding factors. During the mean follow-up time of 22.64 ± 5.84 years in 4,733 individuals, 526 had incident stroke, 432 had ischemic stroke, 530 had incident coronary events (CE), 339 had incident heart failure (HF), 320 had incident chronic kidney disease (CKD) and 1,843 individuals died. Hazard ratio (HR) per standard deviation increase in FST levels adjusted for multiple risk factors was 1.05 (95%CI: 1.00–1.11, p = 0.036) for mortality; 1.10 (95%CI: 1.00–1.20, p = 0.042) for stroke; 1.13 (95%CI: 1.03–1.25, p = 0.014) for ischemic stroke; 1.16 (95%CI: 1.03–1.30, p = 0.015) for HF; and 1.38 (95%CI: 1.12–1.70, p = 0.003) for a diagnosis of CKD. In MDC-CC individuals without prevalent or incident diabetes, the association between FST and stroke, CE and CKD remained significant; but not with mortality or HF. Conclusions: Elevated circulating FST associates with an increased risk of mortality and HF, which partly may be mediated by diabetes. FST also associated with stroke, ischemic stroke, CE and CKD, independently of established risk factors including diabetes.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Chronic kidney disease, Coronary events, Follistatin, Heart failure, Ischemic stroke, Mortality, Stroke
in
Nutrition, Metabolism and Cardiovascular Diseases
publisher
Elsevier
external identifiers
  • pmid:38000997
  • scopus:85179698016
ISSN
0939-4753
DOI
10.1016/j.numecd.2023.09.012
language
English
LU publication?
yes
id
1e14a737-f2a4-4803-a8f8-7ae6f780282d
date added to LUP
2024-01-10 11:52:40
date last changed
2024-04-25 07:51:52
@article{1e14a737-f2a4-4803-a8f8-7ae6f780282d,
  abstract     = {{<p>Background and aims: Previous study showed that elevated circulating hepatokine follistatin (FST) associates with an increased risk of type 2 diabetes by inducing adipose tissue insulin resistance. Here we explore further the relationships between plasma FST levels with mortality and health outcomes. Methods and results: The population-based Malmö Diet Cancer cardiovascular cohort (n = 4733, age 45–68 years) was used to study plasma FST in relation to incidence of health outcomes, by linkage with national patient registers. Cox regression analysis was used to assess the associations of plasma FST and outcomes, with adjustments for multiple potential confounding factors. During the mean follow-up time of 22.64 ± 5.84 years in 4,733 individuals, 526 had incident stroke, 432 had ischemic stroke, 530 had incident coronary events (CE), 339 had incident heart failure (HF), 320 had incident chronic kidney disease (CKD) and 1,843 individuals died. Hazard ratio (HR) per standard deviation increase in FST levels adjusted for multiple risk factors was 1.05 (95%CI: 1.00–1.11, p = 0.036) for mortality; 1.10 (95%CI: 1.00–1.20, p = 0.042) for stroke; 1.13 (95%CI: 1.03–1.25, p = 0.014) for ischemic stroke; 1.16 (95%CI: 1.03–1.30, p = 0.015) for HF; and 1.38 (95%CI: 1.12–1.70, p = 0.003) for a diagnosis of CKD. In MDC-CC individuals without prevalent or incident diabetes, the association between FST and stroke, CE and CKD remained significant; but not with mortality or HF. Conclusions: Elevated circulating FST associates with an increased risk of mortality and HF, which partly may be mediated by diabetes. FST also associated with stroke, ischemic stroke, CE and CKD, independently of established risk factors including diabetes.</p>}},
  author       = {{Pan, Jingxue and Nilsson, Jan and Engström, Gunnar and De Marinis, Yang}},
  issn         = {{0939-4753}},
  keywords     = {{Chronic kidney disease; Coronary events; Follistatin; Heart failure; Ischemic stroke; Mortality; Stroke}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Nutrition, Metabolism and Cardiovascular Diseases}},
  title        = {{Elevated circulating follistatin associates with increased risk of mortality and cardiometabolic disorders}},
  url          = {{http://dx.doi.org/10.1016/j.numecd.2023.09.012}},
  doi          = {{10.1016/j.numecd.2023.09.012}},
  year         = {{2023}},
}