GRAPHICAL ABSTRACT

INTRODUCTION

As population aging is recognized as a global issue of increasing importance, the timely detection and intervention of early vascular aging is critical for the primary prevention of cardiovascular disease (CVD). With advancing age, arteries become stiffer, which not only increases the risk of CVD but also leads to significant organ damage, including cognitive dysfunction, heart failure, atrial fibrillation, and renal dysfunction [1–3]. Thus, brachial-ankle pulse wave velocity (baPWV), a composite measure of central and peripheral arterial stiffness, has emerged as a noninvasive, convenient, valid, and reliable method suitable for population-based screening of vascular aging. Current guidelines recommend the measurement of baPWV for cardiovascular (CV) risk stratification [1,3–5].

During aging, significant changes occur in body composition [6,7]. Lipids are redistributed from subcutaneous adipose tissue to visceral adipose and muscle tissues, leading to visceral obesity and myosteatosis. As visceral obesity and myosteatosis progress, the associated lipotoxicity, chronic inflammation, and insulin resistance create a vicious cycle that further contributes to the development of sarcopenic obesity, overt sarcopenia, and vascular aging [7,8]. Thus, myosteatosis has recently been conceptualized as a form of ‘proto-sarcopenia’ representing an early stage in the progression toward full-blown sarcopenia [7,9,10]. Therefore, early assessment of muscle quality and visceral fat accumulation before the onset of full-blown sarcopenia is critical for the timely diagnosis and intervention of metabolic alterations. However, while previous studies have shown that reduced muscle mass, sarcopenia [11–15], or visceral obesity are associated with increased arterial stiffness [16,17], precise evaluation of myosteatosis through the subdivision of muscle area has been lacking.

To evaluate myosteatosis and visceral adiposity, computed tomography (CT) has emerged as the gold standard due to its precision in differentiating and quantifying muscle and adipose tissues [6,7]. In our recent study, we segmented the CT-measured total abdominal muscle area (TAMA) into three components: normal attenuation muscle area (NAMA), which indicates healthy muscle; low attenuation muscle area (LAMA), representing lipid-infiltrated muscle; and intermuscular adipose tissue (IMAT), denoting fat tissue located between muscle groups [6]. We proposed the NAMA/TAMA index as an accurate measure of muscle quality, where a lower value signifies a decreased proportion of healthy muscle (NAMA) and an increased infiltration of myosteatosis (LAMA and IMAT) [6]. In addition, we previously reported that myosteatosis (decreased NAMA/TAMA index) was associated with various metabolic disorders [18–21]. However, the relationship between myosteatosis and arterial stiffness, particularly in conjunction with visceral obesity, has yet to be investigated.

Therefore, we aimed to evaluate whether myosteatosis and visceral obesity are associated with increased arterial stiffness as measured by baPWV, in a population without known CVD.

METHODS

Study population

This was a retrospective cross-sectional study involving individuals who voluntarily underwent simultaneous abdominal CT scans and baPWV assessments between 2012 and 2013 at the Health Screening and Promotion Center in Asan Medical Center (Seoul, Korea) (n=6,410). To analyze the association between ectopic fat infiltration and baPWV in a primary prevention setting, we excluded participants with a history of CVD, including myocardial infarction, congestive heart failure, and/or cerebrovascular accidents (n=202). We further excluded participants with a history of cancer or a diagnosis of incident cancer during the health examination (n=177), and an ankle-brachial index (ABI) ≤0.9 and/or >1.4 (to ensure the accuracy of baPWV measurements [n=27]) [1]. After excluding ineligible subjects, 6,004 subjects without known CVD were included. This study was approved by the Ethics Committee/Institutional Review Board at Asan Medical Center (IRB No. 2021–0517). Written informed consent from the patients was waived due to the retrospective nature of our study.

Clinical assessment

All study subjects completed a questionnaire regarding their medical history, medication use, exercise habits, alcohol consumption, and smoking habits. Diabetes was defined as a fasting plasma glucose (FPG) level of ≥7.0 mmol/L or a glycated hemoglobin (HbA1c) level of ≥6.5% [22]. Additionally, subjects taking anti-diabetic medication were classified as having diabetes. Hypertension was defined as a systolic/diastolic blood pressure (BP) of ≥140/90 mm Hg or a history of antihypertensive medication use. A family history of premature CVD was defined as the occurrence of CVD in first-degree relatives before the age of 55 for men or 65 for women [23]. Physical activity was assessed using the validated Korean version of the International Physical Activity Questionnaire (IPAQ) and was converted to metabolic equivalent task minutes per week (MET-min/wk) according to the IPAQ scoring protocol [24]. Regular aerobic exercise was defined as ≥30 minutes of moderate-intensity activity on ≥5 days/week or ≥20 minutes of vigorous-intensity activity on ≥3 days/week [25]. Regular resistance exercise was defined as resistance training ≥3 days/week [26]. Smoking status was categorized as never, former, or current smoker. Smoking pack-years were calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the individual has smoked. Beverage-specific alcohol consumption was calculated in grams per day based on the alcohol content, frequency of consumption, and quantity consumed [27]. Menopausal status was classified as premenopausal, postmenopausal, or surgical menopausal (i.e., menopause induced by hysterectomy with or without oophorectomy).

Anthropometric and laboratory measurements

Height and weight were measured in subjects wearing light clothing and without shoes. Body mass index (BMI) was calculated by dividing weight in kilograms by the square of height in meters. Waist circumference (WC) was measured midway between the costal margin and the iliac crest at the end of a normal expiration. BP was measured on the right arm after a rest period of at least 5 minutes, using an automatic manometer with an appropriately sized cuff. After an overnight fast, early morning venous blood samples were collected and analyzed at a central, certified laboratory at Asan Medical Center. Fasting total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), uric acid, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were measured using enzymatic colorimetric methods with a Toshiba 200FR Neo analyzer (Toshiba Medical System Co. Ltd., Tokyo, Japan). Gamma-glutamyltransferase (GGT) levels were measured using the L-γ-glutamyl-p-nitroanilide method (Toshiba). Creatinine levels were measured using the Jaffe method, and estimated glomerular filtration rates (eGFRs) were calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [28]. FPG was measured using the hexokinase method, while high-sensitivity C-reactive protein (hsCRP) was measured using the immunoturbidimetric method with the Toshiba 200FR Neo analyzer (Toshiba Medical System Co. Ltd.). Insulin concentrations were determined with an immunoradiometric assay (TFB, Tokyo, Japan). Ion-exchange high-performance liquid chromatography (Bio-Rad Laboratories Inc., Hercules, CA, USA) was used to measure HbA1c levels. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as the product of fasting insulin (μU/mL) and FPG (mmol/L) levels, divided by 22.5. All enzymatic activities were measured at 37°C.

Measurement of baPWV

ABI and baPWV were assessed using an automatic device (VP-2000, Colin, Komaki, Japan) after the subjects had rested for at least 5 minutes. Electrodes were placed on both wrists, and the cuffs were wrapped around the brachia and ankles. After simultaneous measurement of BP and waveforms in all four limbs, the time interval between the brachial and ankle waveforms (ΔTba) was determined. The distance between the brachium and the ankle (La–Lb) was estimated automatically according to the subject’s height. After collecting these data, baPWV was calculated using the following equation: baPWV=(La−Lb)/ΔTba (in cm/sec). After measurement of the right and left baPWV, the mean baPWV was calculated and used as a marker of arterial stiffness. The measurement of baPWV was categorized as normal (<1,400 cm/sec) or elevated (≥1,400 cm/sec) according to current guidelines [1,29] and previous studies [2,30] predicting CVD risk, especially in the low-risk group.

Assessment of abdominal visceral obesity and skeletal muscle quality

Abdominal CT examinations were performed using the Somatom Definition (Siemens Healthineers, Erlangen, Germany), Discovery CT750 HD (GE Healthcare, Milwaukee, WI, USA), or LightSpeed VCT scanner (GE Healthcare). For contrast enhancement, 100–150 mL of iopromide (Ultravist 370 or Ultravist 300, Bayer Schering Pharma, Berlin, Germany) was intravenously administered. Body composition was assessed using abdominal CT in conjunction with automated artificial intelligence software developed through a fully convolutional network segmentation technique. The software automatically selected axial CT slices at the inferior endplate level of the L3 vertebra. Subsequently, the selected CT images were automatically segmented to delineate the boundaries of the muscle area, visceral fat area (VFA), and subcutaneous fat area (SFA). An image analyst and a radiologist, both blinded to the clinical information of the subjects, reviewed all selected CT slices and segmented areas.

The abdominal VFA was delineated using fat tissue thresholds (−190 to −30 Hounsfield unit [HU]) [31]. The visceral-to-subcutaneous fat ratio (VSR) was calculated by dividing VFA by the SFA. For the evaluation of muscle quality, the cross-sectional areas of selected axial muscle images (i.e., psoas, paraspinal, transversus abdominis, rectus abdominis, quadratus lumborum, and internal and external obliques) were further segmented based on predetermined HU thresholds as follows: (1) NAMA (30 to 150 HU), reflecting healthy muscle with minimal intramuscular fat, (2) LAMA (−29 to 29 HU), reflecting unhealthy muscle with an intramuscular lipid pool, and (3) IMAT (−190 to −30 HU), reflecting the apparent fat tissue located between muscle groups and muscle fibers [32]. TAMA (−190 to 150 HU) was defined as the total area encompassing all skeletal muscles and fat tissues (TAMA=NAMA+LAMA+IMAT). As a representative index of muscle quality, we also calculated the NAMA/ TAMA index (NAMA/TAMA×100), where a lower value indicates a decreased proportion of healthy muscle (NAMA) and an increased proportion of myosteatosis (LAMA and IMAT).

Considering the significant differences in body composition between sexes, visceral obesity was defined as a VFA of ≥130 cm² in men and ≥85 cm² in women [31]. Myosteatosis was defined as a NAMA/TAMA index of <66.4 in men and <65.1 in women, using a T-score of <−2.0 as the cut-off point [6].

Statistical analysis

Statistical analyses were performed separately for each sex considering the differences in visceral fat composition and myosteatosis [6,31,33]. Men and women were further divided into subgroups based on baPWV categories or sex-specific cut-off values for VFA and the NAMA/TAMA index. Continuous variables with normal distributions are presented as mean±standard deviation, while continuous variables with skewed distributions are presented as median (interquartile range). Categorical variables are expressed as numbers and percentages. The characteristics of the study population were compared according to baPWV, VFA, and NAMA/TAMA index categories, using independent t-tests or the Mann-Whitney U test for continuous variables and the chi-squared test for categorical variables. To assess the independent associations of visceral obesity and myosteatosis with arterial stiffness, multivariate logistic regression analysis was used to calculate odds ratios (ORs).

The following adjustment models were applied: Model 1 was adjusted for visceral obesity (assessed by VFA) or myosteatosis (assessed by the NAMA/TAMA index), meaning that visceral obesity was adjusted for myosteatosis or vice versa. Model 2 included additional adjustments for age, smoking pack-years, alcohol consumption, total METs, regular resistance exercise, hypertension, diabetes, use of lipid-lowering medications, family history of CVD, and menopausal status (adjusted only for women). Model 3 included further adjustments for laboratory values, including LDL-C, HDL-C, hsCRP, and HOMA-IR. Statistical analyses were performed using SPSS version 21.0 for Windows (SPSS Inc., Chicago, IL, USA). P values less than 0.05 were considered statistically significant.

RESULTS

Characteristics according to baPWV categories

The mean age of the 6,004 subjects was 53.8±8.3 years; 61.6% were male, and the mean BMI was 24.1±3.0 kg/m². The vast majority of study subjects, 99.7% (5,988/6,004), had eGFRs of ≥60 mL/min/1.73 m², and the remaining 0.3% (16/6,004) had a median eGFR of 57 mL/min/1.73 m² (interquartile range, 53 to 58). Among the total population, 38.4% (n=2,306) showed elevated baPWV (≥1,400 cm/sec), including 38.1% (n=1,408) of men and 38.9% (n=898) of women. Tables 1 and 2 present the differences in baseline characteristics according to baPWV categories for men and women. In both sexes, subjects in higher baPWV categories were significantly older, had a greater number of pack-years of smoking, showed a higher prevalence of diabetes and hypertension, and were more likely to use lipid-lowering medications. They also displayed unfavorable metabolic parameters, including higher BP, FPG, HbA1c, TG, AST, ALT, GGT, hsCRP, HOMA-IR, and WC. Women in higher baPWV categories had a higher BMI, while men showed no significant differences. Regarding fat and muscle quality indices based on abdominal CT scans, both men and women with higher baPWV exhibited significantly higher VFA and VSR. They also showed significantly lower NAMA and NAMA/TAMA indices, along with higher LAMA and IMAT indices.

Characteristics according to VFA and NAMA/TAMA values

We divided men and women according to sex-specific cut-off points for VFA and NAMA/TAMA values (Tables 3, 4). Men exhibited a significantly higher prevalence of visceral obesity compared to women (56.1% vs. 33.8%, P<0.001). Both men and women with higher VFA had a greater number of pack-years of smoking, a higher prevalence of diabetes and hypertension, and were more likely to use lipid-lowering medications. They also displayed unfavorable metabolic profiles, including higher BP, FPG, HbA1c, TG, LDL-C, uric acid, AST, ALT, GGT, hsCRP, HOMA-IR, BMI, WC, VSR, and lower HDL-C levels. Men with higher VFA showed greater alcohol consumption and were less likely to engage in regular aerobic and resistance exercises, as well as physical activity. Women with higher VFA were significantly older and more likely to be postmenopausal. In both men and women, individuals with higher VFA showed higher LAMA and IMAT indices, along with a lower NAMA/TAMA index. They also showed significantly elevated baPWV values and a higher prevalence of increased baPWV (≥ 1,400 cm/sec), regardless of sex.

When we divided the subjects using sex-specific cut-off points for NAMA/TAMA values, as described in the methods section, women exhibited a significantly higher prevalence of myosteatosis compared to men (11.3% vs. 29.4%, P<0.001). Both men and women with myosteatosis (indicated by a lower NAMA/ TAMA index) were significantly older. Subjects with myosteatosis also demonstrated a higher prevalence of diabetes and hypertension and were more likely to use lipid-lowering medications. They exhibited unfavorable metabolic profiles, including higher BP, FPG, HbA1c, GGT, hsCRP, HOMA-IR, and lower HDL levels. They showed lower levels of physical activity and higher BMI, WC, VFA, SFA, and VSR. They also exhibited lower NAMA and higher LAMA and IMAT indices. Regardless of sex, individuals with myosteatosis showed significantly higher baPWV values than those without, as well as a higher prevalence of baPWV values ≥1,400 cm/sec.

Association of visceral obesity and myosteatosis with baPWV

To assess the association of visceral obesity and myosteatosis with baPWV, multivariate logistic regression analysis was applied, and ORs and 95% confidence intervals (CIs) for elevated baPWV (≥1,400 cm/sec) were calculated (Table 5). In the unadjusted model, the ORs for elevated baPWV were significantly higher in groups with visceral obesity, regardless of sex. When we adjusted for myosteatosis (model 1), the ORs in subjects with visceral obesity remained significantly higher in both men and women. After further adjustments (models 2, 3), the ORs consistently remained elevated in men with statistical significance but were attenuated in women with visceral obesity. In the fully adjusted model, which included various clinical and laboratory metabolic risk factors (model 3), the ORs were 1.32 (95% CI, 1.10 to 1.60) in men (P=0.004) and 1.24 (95% CI, 0.38–4.04) in women (P=0.723).

When we analyzed the association between myosteatosis and baPWV, both men and women with myosteatosis showed significantly increased ORs for elevated baPWV in the unadjusted model. After adjusting for visceral obesity (model 1), the ORs remained significantly higher in both sexes; however, they became non-significant after further adjustments in models 2 and 3 for men. In contrast, women with myosteatosis consistently showed higher ORs for elevated baPWV across various adjusted models (models 2 and 3). In the fully adjusted model (model 3), the ORs for elevated baPWV were 3.26 (95% CI, 1.13 to 9.44) in women (P=0.029), and 0.85 (95% CI, 0.65 to 1.10) in men (P=0.213). We conducted an additional analysis stratifying women by menopausal status (Supplemental Table S1). Among premenopausal women, the association between ectopic fat deposition and elevated baPWV was no longer significant after adjustment. In contrast, among postmenopausal women, myosteatosis remained significantly associated with elevated baPWV, with an OR of 23.05 (95% CI, 3.63 to 146.52) in the fully adjusted model 3 (P=0.001).

DISCUSSION

In this study, we found that ectopic fat infiltration, including visceral obesity and myosteatosis, was significantly associated with increased arterial stiffness. After adjusting for multiple CVD risk factors, visceral obesity was significantly associated with elevated baPWV, particularly in men, while myosteatosis showed a significant association in women. To our knowledge, this is the first study to demonstrate that myosteatosis, as indicated by a low NAMA/TAMA index segmented by abdominal CT, in conjunction with visceral obesity, is associated with increased baPWV.

This study demonstrates that the types of ectopic fat deposition affecting arterial stiffness vary by sex. After adjustments, visceral obesity was found to increase the risk of arterial stiffness in men, while myosteatosis was significant in women. Although the underlying reasons remain unclear, the relatively higher prevalence of visceral obesity in men and myosteatosis in women may contribute to these differences. Men are known to accumulate more abdominal visceral fat due to the effect of testosterone [34]. Accordingly, despite applying a higher sex-specific cut-off for VFA in men (≥130 cm² vs. ≥85 cm² in women), its prevalence was significantly higher in men than in women (56.1% vs. 33.8%, P<0.001), potentially amplifying its adverse impact on arterial stiffness. Similarly, although a lower NAMA/TAMA index cut-off value for myosteatosis was applied in women (<65.1) than in men (<66.4), a greater proportion of subjects was classified below this threshold (men vs. women; 11.3% vs. 29.4%, P<0.001), which may have made the harmful effects of myosteatosis more pronounced in women. Additionally, since the majority of women in our study were postmenopausal (70.9%), declining estrogen levels may contribute to a decrease in muscle mass [35,36]. Previously, we also demonstrated that the prevalence of myosteatosis, defined by the same criterion used in this study (NAMA/TAMA T-score <–2) increases rapidly in postmenopausal women [37]. Furthermore, compared to men, women have a relatively higher proportion of type I muscle fibers [38], which possess greater oxidative capacity and tend to accumulate more intramyocellular lipids with aging [36]. Therefore, in post- or perimenopausal women with decreased estradiol levels, the reduced mitochondrial function and regenerative capacity of type I muscle fibers [35,39] along with increased muscular fat deposition [36], may lead to more deleterious effects of myosteatosis compared to men. In line with this, when we conducted an additional analysis stratified by menopausal status, myosteatosis was more significantly associated with elevated baPWV in the postmenopausal group (Supplemental Table S1).

As aging progresses, arterial stiffening leads to an increase in systolic and pulse BP, thereby elevating cardiac afterload [1,3]. This heightened afterload contributes to left ventricular hypertrophy and heart failure, while also diminishing coronary perfusion [1,3]. Furthermore, impaired arterial buffering results in the excessive transmission of pulsatile energy to target organs, including the brain, kidneys, and heart, ultimately causing end-organ damage [1,3]. Pulse wave velocity (PWV) is the gold standard method for assessing arterial stiffness, and among its various modalities, the baPWV measures both central and peripheral arterial stiffness [1,3]. Notably, baPWV is easy to measure, highly reliable and reproducible, noninvasive, and free from radiation exposure, making it an advantageous tool for population-based screening in clinical practice [3]. Several studies have demonstrated that an increase in baPWV is associated with a heightened risk of CV events, CV mortality, and all-cause mortality [40–42]. Furthermore, when baPWV was incorporated into a CVD prediction model, net reclassification improved by approximately 25% [41]. In addition, the study reported that baPWV significantly predicted future CVD events in both individuals with and without hypertension; however, the predictive strength was stronger in those without hypertension, suggesting that baPWV plays an important role in assessing future CVD risk in low-risk populations [41]. The current Japanese Atherosclerosis Society guidelines propose baPWV cutoffs: normal (<1,400 cm/sec), borderline (1,400–1,800 cm/sec), and abnormal (>1,800 cm/sec) [29]. A prior study that informed these guidelines indicated that a baPWV ≥1,400 cm/sec is an independent predictor for distinguishing patients with atherosclerotic CVD, particularly in the general population [30]. Although we adopted an elevated PWV cut-off (≥1,400 cm/sec) based on existing guidelines and previous studies [1,29,30,43], further research is needed to determine whether this threshold is applicable across different ethnic populations.

During aging, adipose inflammation leads to the redistribution of fat to the intra-abdominal area (visceral fat) and fatty infiltrations in skeletal muscles [6,7]. The deposition of intramyocellular lipids further promotes lipotoxicity, which induces and exacerbates mitochondrial dysfunction, oxidative stress, insulin resistance, and inflammation [7]. These molecular changes interact with one another, creating a vicious cycle that contributes to sarcopenic obesity and vascular aging [7,8]. Importantly, recent studies have reported that myosteatosis precedes muscle atrophy even before sarcopenia is diagnosed [7,10]. Although previous studies have demonstrated an association between sarcopenia and arterial stiffness [11–15], they had limitations in that muscle quality was not evaluated, and the analyses were primarily restricted to older populations. In this regard, our study is strengthened by the simultaneous measurement of myosteatosis and visceral fat in a relatively younger population, allowing us to analyze the association between ectopic fat infiltration and arterial stiffness. Our results indicate that subjects with a lower NAMA/TAMA index (myosteatosis) or higher VFA showed unfavorable metabolic characteristics and a higher prevalence of elevated baPWV. For the timely diagnosis and intervention of metabolic changes before the onset of sarcopenia, early assessment of muscle quality and visceral fat using opportunistically obtained CT images may be crucial in preventing vascular aging [7,8].

Our study has several limitations. First, the cross-sectional design does not permit causal inference or clarification of the underlying pathophysiological mechanisms linking myosteatosis, visceral obesity, and arterial stiffness. A decline in muscle mass reduces energy expenditure and exacerbates insulin resistance, thereby promoting ectopic fat accumulation [7]. The subsequent increase in ectopic fat further aggravates insulin resistance and systemic inflammation, leading to muscle atrophy and establishing a vicious cycle of metabolic deterioration that contributes to the progression of arterial stiffness [17]. In addition, arterial stiffness reduces blood flow, resulting in further loss of muscle mass [44]. In line with this, our study demonstrated that individuals with myosteatosis exhibited a high prevalence of visceral obesity and elevated PWV, while those with visceral obesity also showed a high prevalence of myosteatosis and elevated PWV. However, due to the cross-sectional design, it was difficult to establish a definitive causal relationship. Second, we did not evaluate appendicular muscle quality or muscle strength, both of which are important determinants in diagnosing sarcopenia and are closely linked to metabolic disorders [12–15]. Lastly, as our study was conducted among Korean men and women who voluntarily underwent simultaneous abdominal CT scans and baPWV assessments during routine health examinations, selection bias may have occurred, limiting the generalizability of our findings to other populations or ethnicities.

However, our study also has several strengths. First, we specifically divided the CT-measured abdominal muscle area into good-quality (NAMA) and poor-quality (LAMA and IMAT) components, and we assessed VFA in a relatively large cohort of subjects (n=6,004). Unlike previous studies that merely evaluated the quantity of muscle or visceral obesity [16,17], our study offers the advantage of accurately assessing muscle quality by subdividing the muscle area on CT images. Second, to elucidate the clinical significance of ectopic fat infiltration in relatively healthy individuals suitable for a primary prevention setting, we excluded participants with a history of CVDs—such as myocardial infarction, congestive heart failure, and/or cerebrovascular accidents—as well as those with a history of cancer. Furthermore, by excluding individuals with an ABI of ≤0.9 or >1.4, we minimized the potential inaccuracies in PWV measurements caused by arterial obstruction or vascular calcification [3]. Third, considering the established differences in muscle mass and ectopic fat deposition between men and women [6,18], we conducted separate analyses by sex. Men are reported to have a significantly higher peak muscle mass and tend to accumulate more abdominal visceral fat compared to women [34,45]. Given the variations in adipose tissue distribution and muscle mass influenced by sex hormones and lifestyle risk factors [34], it is appropriate to perform sex-specific analyses. Lastly, we adjusted for multiple metabolic risk factors likely associated with arterial stiffness, including age, smoking, alcohol consumption, physical activity levels, resistance exercise, diabetes, hypertension, use of lipid-lowering medications, family history of CVD, menopausal status, LDL-C, HDL-C, hsCRP, and HOMA-IR. Notably, we adjusted for visceral fat adiposity in the group with myosteatosis and for myosteatosis in the group with visceral fat adiposity, allowing us to analyze which type of ectopic fat accumulation exerts a more significant influence on arterial stiffness according to sex. In conclusion, our study demonstrated that both visceral obesity and myosteatosis were significantly associated with increased arterial stiffness in a primary prevention setting. After adjusting for all potential CV risk factors, visceral obesity remained significantly associated with arterial stiffness in men, whereas myosteatosis showed a significant association in women. Timely screening of individuals at risk for sarcopenic obesity, along with the implementation of effective preventive strategies, may help delay the progression of vascular aging and CVDs. Further well-designed interventional studies aimed at improving myosteatosis and visceral obesity are warranted to elucidate the causal role of ectopic fat deposition in the prevention of arterial stiffness.

Supplementary Information

Article information

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

ACKNOWLEDGMENTS

We thank Prof. Namkug Kim from the Department of Convergence Medicine at Asan Medical Center for developing the automated artificial intelligence software used for abdominal CT segmentation. Also, we thank Dr. Joon Seo Lim from the Scientific Publications Team at Asan Medical Center for his editorial assistance in preparing this manuscript.

AUTHOR CONTRIBUTIONS

Conception or design: M.J.L., H.K.K. Acquisition, analysis, or interpretation of data: M.J.L., H.K.K., S.H.L. Drafting the work or revising: M.J.L., H.K.K., E.H.K., S.J.B., H.J.N., C.H.J., W.J.L. Final approval of the manuscript: M.J.L., H.K.K., E. H.K., S.J.B., H.J.N., S.H.L., C.H.J., W.J.L.

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