Skeletal muscle and adipose tissue are the two largest endocrinal organs in the body, responsible for various molecules synthesis, namely, myokines and adipokines1. Both types of molecules act directly in several metabolic processes and can contribute directly to endothelial function and vascular remodeling2,3. Endothelial function and arterial stiffness can be measured with pulse wave velocity (PWV)4. This study aims to correlate the PWV with skeletal muscle and adipose tissue characteristics in patients with peripheral arterial disease (PAD).
An observational, prospective, and longitudinal study was conducted from january 2018 to december 2021. This research project included patients with PAD suggested by clinical history and objective examination and confirmed with ankle-brachial index. An informed written consent was obtained. The study was approved by the ethical committee of the local Hospital (75/2017). The clinical characteristics and the cardiovascular risk were registered. The anthropometric measures were recorded (weight, height, body mass index and hip and waist perimeter). The quantity of adipose tissue (visceral, subcutaneous and total) and of skeletal muscle were determined with a CT scan at the lower border of the third lumbar vertebra. The skeletal mass was also determined. A radiologist and a vascular surgeon blinded to the subject's characteristics traced the different compartments of adipose tissue and muscle. The area of adipose tissue and skeletal muscle and density (mass) were semi-automatically determined using Fiji (Fiji is just ImageJ), an open-source image processing package based on ImageJ®.15The strength (the muscle function) was measured with a Jamar hydraulic dynamometer. SphygmoCor® was used to measure PWV, (three readings were taken and the average was used for analysis). A probe measured the pressure at the right cervical carotid artery and the right femoral artery at the inguinal level. The distance between these two points was manually determined from the suprasternal angle to the femoral artery. Continuous variables were expressed as the mean ± standard deviation and as the percentage for categorical variables. The Shapiro-Wilk test was used to assess all continuous variables for normality. Continuous variables between two groups were compared with Student's t-test or with Mann-Whitney. Spearman correlation was utilized to adjust for potential confounding variables.
A p-value of less than .05 was considered significant. Statistical evaluation was performed using SPSS software, version 20.0 (SPSS, Inc., Chicago, IL, USA).
116 patients, 81.03% men (mean age: 67.659.53 years-old) 64% with claudication and 46% with critical limb threatening ischaemia (CLTI) were enrolled. Patients with CLTI had a significantly higher PWV (Claudicants: 10.52±3,19m/s versus CLTI: 13.74±4,36m/s p=0.012). No difference was identified between PWV and presence of cardiovascular risk factors. There was a moderate and a positive correlation between PWV and age (rs=0.481; p=0.000) and between PWV and systolic arterial pressure (right arm rs=-0.325; p=0.009; left arm rs=-0.255 p=0.045). The area of total adipose tissue and visceral adipose tissue (determined with CT scan) were moderately and positively correlated with arterial stiffness (rs= 0,380 p=0.012 and rs = 0,320 p=0.036, respectively) (Fig.1). No correlation was found between subcutaneous adipose tissue or anthropometric measures and PWV. A moderate and negative correlation was found between strength and PWV (rs = -0,402 p=0.007) (Fig.2). No association was found between skeletal muscle mass or area and PWV.
In this study, the adiposity, mainly visceral obesity was associated with arterial stiffness in patients with PAD. No association was found between the quantity of subcutaneous adipose tissue and PWV. These results can be explained by the pro-inflammatory secretory profile of the visceral fat, that increases the peripherical sympathetic activity, the vascular remodeling and consequently the arterial stiffness2,3. Subcutaneous fat, on the other hand, has a cardiovascular protective role5. We also found an inverse correlation between strength and arterial dysfunction as previously described in non-PAD populations6. Patients with CLTI have a higher PWV (as expected). We registered a mean value of 13.74±4,36m/s in CLTI patients. A PWV > 10m/s is associated with an increase cardiovascular mortality, which can help to explain the worse prognosis in these patients. Pharmacological treatment and physical exercise programs may contribute to optimize the adipose tissue and skeletal muscle function and consequently minimize the cardiovascular risks.
1-F. Li, Y. Li, Y. Duan, C. A. A. Hu, Y. Tang, and Y. Yin, "Myokines and adipokines: Involvement in the crosstalk between skeletal muscle and adipose tissue," Cytokine Growth Factor Rev., vol. 33, pp. 73-82, 2017, doi: 10.1016/j.cytogfr.2016.10.003.
2-Choi KM. The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis. Endocrinology and Metabolism 2016;31:1-6
3-Nosalski R, Guzik TJ. Perivascular adipose tissue inflammation in vascular disease. Br J pharmacology. 2017 Oct;174(20):3496-351
4- Mendes-Pinto D, Rodrigues-Machado MG. Applications of arterial stiffness in peripheral arterial disease. J Vasc Bras 2019.
5- Porter SA, Massaro JM, Hoffmann U, Vasan RS, O'Donnel CJ, Fox CS. Abdominal subcutaneous adipose tissue: a protective fat depot? Diabetes Care 2009 Jun; 32(6): 1068-1075.
6-Aminddin A, Hashim MFN, Zaberi NASM, Wei LZ, Chu BC, Jamaludin NA et al. The association between arterial stiffness and muscles indices among healthy subjects and subjects with cardiovascular risk factors: an evidence-based review. Front Physiol, 23 November 2021.