Research Article: Association between GDF-15 levels and changes in vascular and physical function in older patients with hypertension

Date Published: October 12, 2016

Publisher: Springer International Publishing

Author(s): Maryam Barma, Faisel Khan, Rosemary J. G. Price, Peter T. Donnan, C. Martina Messow, Ian Ford, Alex McConnachie, Allan D. Struthers, Marion E. T. McMurdo, Miles D. Witham.


Growth differentiation factor-15 (GDF-15) may be a biomarker of disease, protective response and/or prognosis, in older people with hypertension.

To correlate baseline GDF-15 levels with physical and vascular health data in this population.

Baseline blood samples were analysed using a GDF-15 ELISA assay kit. Correlations with baseline and 12-month outcome data, including measures of physical and vascular function, were performed.

A total of 147 individuals, mean age 76.8 ± 4.7 years, were included. 77 (52 %) were male. Baseline log10GDF-15 showed significant correlations with age (r = 0.37, p < 0.001), total cholesterol (r = −0.33, p < 0.001) and 6-min walking distance (r = −0.37, p < 0.001). Age remained significantly associated with log10GDF-15 in multivariable analysis (beta = −0.29, p = 0.001). Baseline log10GDF-15 was significantly associated with decline in 6-min walk distance over 12 months (beta = −0.27, p = 0.01) in multivariable models. No significant correlations were seen with changes in vascular function over 12 months. Baseline GDF-15 predicts declining physical, but not vascular, function in our population.

Partial Text

The decline in physical function that commonly accompanies ageing is multifactorial in aetiology. Impairments in multiple organ systems, including muscle, nerve, bone, blood vessels and the brain, all contribute to this loss in function. Cardiovascular disease (CVD) in particular is a common cause of hospital admissions amongst older patients and is also a key driver of functional decline. Functional loss, and the accompanying vulnerability to stressors, is captured in the concept of frailty [1]. It is clear that in order to effectively manage frailty, an approach that protects, or bolsters function, across multiple organ systems—i.e. an approach that builds resilience—is necessary [2]. For such an approach to be practical, interventions that target common pathologies affecting multiple organ systems are required; targets such as chronic inflammation, oxidative stress and mitochondrial dysfunction are examples of this. Both CVD and sarcopenia (the age-related decline in muscle function) have been linked to chronic inflammation. Effective interventions may be best deployed early in the process of decline, and to detect those at risk, markers that predict decline before the onset of frailty would be useful.

We conducted analyses using samples and data collected prospectively as part of the vitamin D in isolated systolic hypertension (VitDISH) randomised controlled trial, which tested the effect of vitamin D supplementation on blood pressure in patients aged 70 and over with isolated systolic hypertension [10]. Participants were randomised into VitDISH if they had a baseline systolic BP of >140 mmHg but <180 mmHg, a baseline diastolic BP of <90 mmHg and a baseline 25OHD level of <75 nmol/L. Participants received 100,000 units of oral vitamin D3 or placebo every 3 months for a year in the trial, which showed no significant effect of vitamin D supplementation on any outcome measured. The trial was approved by the Fife and Forth Valley National Health Service Research Ethics Committee [10]. Sufficient stored baseline samples were available for 147/159 participants, who had been randomised to VitDISH. Analyses were conducted on 146 of thesσe, as one sample was excluded due to >30 % difference between duplicates on GDF-15 testing. Table 1 shows the baseline population characteristics for these individuals, along with baseline associations between each variable and log10GDF-15 levels. Baseline log10GDF-15 levels were significantly associated with increasing age, total cholesterol levels, diastolic BP and HADS depression scores. Independent sample t-tests showed significantly higher baseline log10GDF-15 in males, and those with a history of diabetes, myocardial infarction and angina. No significant associations were demonstrated with baseline measures of vascular function. Baseline multivariable linear regression showed GDF-15 levels remained associated only with age (beta = 0.29, p < 0.001). Our results suggest that in older patients with hypertension, GDF-15 may be an independent predictor of declining physical function, but does not predict change in vascular function. Whilst our investigation supported previous associations of GDF-15 levels with cardiovascular risk factors and the presence of vascular disease, the responsible mechanisms are not clear, as no correlation was seen between GDF-15 and endothelial function nor arterial stiffness (two key pathophysiological intermediaries for causing vascular disease). Baseline GDF-15 may be associated with walk distance and predicts decline in walk distance, but is not associated with vascular function in older patients with hypertension. These findings may enable the development of new ways to detect those at risk of functional decline, as well as suggesting new pathways to target the inflammatory causes and consequences of ageing.   Source:


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