High follistatin levels may increase risk of HF and mortality
Sweden: A 23-year-long study of more than 4700 middle-aged Swedish adults showed that higher plasma levels of the protein follistatin (FST) are associated with an elevated risk of heart failure (HF) and mortality, which may be partly mediated by diabetes.
Higher follistatin levels were also associated with an increased risk of ischemic stroke, chronic kidney disease (CKD), ischemic stroke and coronary events. These associations were consistent irrespective of diabetes status.
The study was published in Preprints With The Lancet as a preprint and has yet to be peer-reviewed.
Chronic kidney disease is often clinically silent before its diagnosis. Early CKD risk detection could allow at-risk patients to take steps for prevention. Follistatin is shown to be a potential biomarker for detecting CKD risk years before its onset. Previous studies have reported that plasma follistatin was increased up to 19 years before type 2 diabetes onset by inducing adipose tissue insulin resistance, independently of established risk markers for diabetes.
Jingxue Pan, Huazhong University of Science and Technology, China, and colleagues further explored the relationships between plasma FST levels and mortality and health outcomes.
For this purpose, the researchers used a population-based Malmö Diet Cancer cardiovascular cohort comprising 4733 people aged 45-68 years to study plasma follistatin concerning the incidence of health outcomes by linkage with national patient registers. The associations of plasma FST and outcomes were assessed using Cox regression analysis, with adjustments for multiple potential confounding factors.
The study led to the following findings:
- During the mean follow-up time of 22.64±5.84 years in 4,733 individuals, 526 had an incident stroke, 432 had an ischemic stroke, 530 had incident coronary events, 339 had incident heart failure, 320 had incident chronic kidney disease (CKD), and 1,843 individuals died.
- Hazard ratio (HR) per SD increase in FST levels adjusted for multiple risk factors was 1.05 for mortality; 1.13 for ischemic stroke; 1.10 for stroke; 1.16 for HF; and 1.38 for a diagnosis of CKD.
- At entry, the patients' mean follistatin level was 4.78 arbitrary units. Higher levels were significantly associated with diabetes, older age, and higher BMI, systolic blood pressure, waist circumference, total cholesterol, fasting glucose, insulin and triglycerides.
- There was no significant increase in risk for coronary events associated with increasing follistatin levels at baseline.
- Excluding study participants who had diabetes either at baseline or were diagnosed during follow-up changed the adjusted hazard ratios to be insignificant for mortality and heart failure with each standard deviation increase in baseline follistatin, suggesting that diabetes may partly mediate this association. But the risks for the other outcomes remained broadly similar and significant, suggesting that diabetes did not play a substantial role in these outcomes.
"The findings suggest that follistatin may also serve as an independent biomarker for early detection of CKD risk and also of risk for certain other adverse cardiometabolic events," the authors conclude.
Reference:
Pan, Jingxue and Nilsson, Jan and Engström, Gunnar and De Marinis, Yang, Elevated Circulating Follistatin Associates with Increased Risk of Mortality and Cardiometabolic Disorders. Available at SSRN: https://ssrn.com/abstract=4423476 or http://dx.doi.org/10.2139/ssrn.4423476
