Russian Medical Inquiry
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DOI: 10.32364/2587-6821-2022-6-3-120-125

L.I. Alekseeva1,2, E.A. Taskina1, T.A. Raskina3, M.V. Letaeva3, O.S. Malyshenko3, M.V. Koroleva3, Yu.V. Averkieva3, I.I. Grigorieva4

1Research Institute of Rheumatology named after V.A. Nasonova, Moscow, Russian Federation

2Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation

3Kemerovo State Medical University, Kemerovo, Russian Federation

4Kemerovo City Clinical Hospital No. 4, Kemerovo, Russian Federation

Aim: to evaluate the association of sarcopenia and carotid atherosclerosis in elderly male patients with knee osteoarthritis (OA).

Materials and Methods: the study included 36 patients (mean age — 68.9 (66; 71) years) with an established diagnosis of grade II–III knee OA according to the Kellgren-Lawrence scale. Diagnosis of sarcopenia was conducted on the basis of the European Working Group on Sarcopenia in Older People (EWGSOP, 2010) recommendations with the determination of three parameters: muscle strength, muscle mass and muscle function. The severity of carotid atherosclerotic lesions was assessed by duplex color scanning with examination of the intima-media thickness (IMT), the presence of atherosclerotic plaques and the degree of aortic stenosis. Comparative analysis was performed in 3 groups: group 1 — 10 patients without sarcopenia, group 2— 12 patients with presarcopenia, and group 3 — 14 patients with sarcopenia.

Results: IMT in group 3 with sarcopenia was statistically significantly (p=0.005) higher versus the same indicator in men without sarcopenia. The majority (23 (63.9%)) of the patients included in the study had carotid atherosclerotic lesions. The most severe carotid lesion with multiple atherosclerotic plaques and stenosis not less than 50% was significantly more commonly detected in patients with sarcopenia: 35.7% versus group 2 with presarcopenia (8.3%, p=0.015) and without sarcopenia (10.0%, p=0.013). According to the correlation analysis, a significant negative association was established between the severity of carotid atherosclerosis and the musculoskeletal index (r=-0.227, p=0.047).

Conclusion: the association between carotid atherosclerosis and body composition disorders in men with knee OA allows discussing atherosclerosis and sarcopenia as two conditions with common pathogenetic mechanisms that potentially increase the risk of adverse outcomes.

Keywords: sarcopenia, presarcopenia, carotid atherosclerosis, osteoarthritis, elderly, male.

For citation: Alekseeva L.I., Taskina E.A., Raskina T.A. et al. Association of sarcopenia and carotid atherosclerosis in elderly male patients with knee osteoarthritis. Russian Medical Inquiry. 2022;6(3):120–125 (in Russ.). DOI: 10.32364/2587-6821-2022-6-3-120-125.

Background

Cardiovascular diseases resulting from atherosclerosis rank first among chronic non-infectious disorders on the effect on mortality, life expectancy, and quality of life in this nosological group [1]. Overall cardiovascular mortality is estimated to approach 24 million cases annually by 2030. Moreover, almost half of the deaths are due to disorders caused by atherosclerosis [2].

Meanwhile, increased life expectancy and global population aging are important trends of modern demography. The WHO experts predict that the number of people over 65 will be up to 30% of the total world population (or 2 milliard people) by mid-century [3]. Therefore, the development of geriatric medical care is particularly important for modern medicine. The crucial targets of geriatrics are geriatric syndromes, complex multifactorial disorders that emerge in response to age-related impairment in the functioning of organs and systems [4]. Among more than three dozen reported geriatric syndromes, sarcopenia plays a leading role. Its development is associated with a reduced quality of life and increased risk of death. According to the Center for Disease Control and Prevention (CDC), sarcopenia is one of the five major risk factors for morbidity and mortality in persons over 65 [4, 5].

Associations between various conditions, including atherosclerosis and body composition disorders, are now particularly important to customize treatment.

Recent studies have demonstrated a high prevalence of sarcopenia in various cardiovascular diseases. Studies in the past decade suggested that atherosclerotic diseases and body composition disorders have similar risk factors and share common pathogenetic mechanisms [6–11]. Moreover, the combination of these conditions is accounted for by not only age-related degenerative alterations in the human body.

Patients with osteoarthritis (OA) have a higher risk of sarcopenia. It was established that muscle weakness is an important factor determining pain and disability in OA. Reduced muscle mass of the lower limbs is common in OA and increases the risk of falling [12]. Progressive muscle weakness in OA is also associated with muscle fiber atrophy. Meanwhile, some studies suggest a 12%–19% reduction in muscle cross-sectional area in hip and knee OA [13]. Moreover, patients age 60 and over have lower muscle mass or volume than controls [14, 15].

Single studies on the association between sarcopenia and atherosclerosis in elderly and senile patients with knee OA are available, and the findings are conflicting.

Aim

To assess the association between sarcopenia and carotid atherosclerosis in elderly men with knee OA.

Patients and Methods

This cross-sectional study included 36 men over 60 with knee OA (ACR criteria, Kellgren–Lawrence grade 2 and 3).

Exclusion criteria were joint injections over the last six weeks, steroid intake more than three months before the study, knee injuries and/or surgery, and conditions affecting muscle strength and function of the limbs.

The study was approved by the Ethics Committee of the Kemerovo State Medical University. All participants signed an informed consent form.

According to the EWGSOP guidelines (2010) [4], muscle mass, muscle strength, and skeletal muscle functions were measured. Muscle function was measured using the Short Physical Performance Batter. A total score of ≤8 was regarded as a reduction in muscle function. Muscle strength was measured using a hand dynamometer, the best result was evaluated. Muscle mass was measured by multi-slice computed tomography using the Somatom Sensation 64 CT Scanner (Siemens AG Medical Solution, Germany). Reduced muscle mass indicated presarcopenia, whereas reduced muscle mass in association with reduced muscle strength indicated sarcopenia. All patients underwent duplex ultrasound (Sonos 2500, USA) to measure intima–media thickness (IMT), detect atherosclerotic plaques, and evaluate the severity of stenosis.

The grading system of the Russian Cardiology Research and Production Complex (RCRPC) was applied to assess the structural health of the carotid artery wall: 0 (no atherosclerosis), 1 (single atherosclerotic plaque, <50% stenosis), 2 (multiple atherosclerotic plaques, <50% stenosis), 3 (single atherosclerotic plaque, ≥50% stenosis), 4 (multiple atherosclerotic plaques, ≥50% stenosis) [16].

According to the EWGSOP guidelines (2010) [4], patients with OA were divided into three groups: group 1 included individuals without sarcopenia (n=10), group 2 included patients with presarcopenia (n=12), and group 3 included patients with sarcopenia (n=14).

Таблица. Клинико-демографическая характеристика пациентов пожилого возраста с ОА коленного сустава Table. Clinical and demographic characteristics of elderly patients with knee OA

Cardiovascular diseases, i.e., hypertension (n=21, 58.3%) and coronary heart disease (n=17, 47.2%) were the most common comorbidities in elderly patients with knee OA (see Table). In most patients, stable angina pectoris class 2 was diagnosed. Chronic heart failure (CFH) stage 1 was more common in individuals without sarcopenia and patients with presarcopenia than in patients with sarcopenia. Meanwhile, CHF stage 2 was more common in patients with presarcopenia than in patients with sarcopenia. In most patients, CHF class 2 was diagnosed.

Chronic obstructive pulmonary disease (n=13, 36.1%) and digestive disorders, i.e., chronic cholecystitis (n=11, 30.6%), chronic pancreatitis (n=10, 27.8%), and gallstones (n=8, 22.2%), ranked second and third, respectively, among comorbidities in study participants. Kidney diseases, i.e., chronic pyelonephritis (n=8, 22.2%) and kidney stones (n=6, 16.7%) were diagnosed less often.

Statistical analysis was performed using the Statistica v. 6.1.478.0 (StatSoft Inc., USA). All nonparametric variables were represented as a median, first and third quartile (Me (Q1; Q3). Qualitative parameters were represented as absolute and relative (%) indices. Mann–Whitney U test was applied to compare the groups by quantitative parameters. Fisher’s exact test was applied to compare categorical variables. The direction and strength of correlation were assessed using the Spearman’s rank correlation coefficient and multiple linear regression. A p-value less than 0.05 was considered statistically significant.

Results

In most participants (n=28, 77.8%), TIM value was greater than its cutoff value in men over 50 years recommended by the American Society of Echocardiography (2008), i.e., 0.9 mm.

TIM evaluation based on muscular system health has demonstrated that absolute TIM value was 1.2 (1.1; 1.2) mm in men without sarcopenia (р<0.001) and 1.2 (1.1; 1.2) mm in patients with presarcopenia (р<0.001). In patients with sarcopenia, TIM was significantly greater than in men without sarcopenia (р=0.005) and insignificantly greater than in patients with presarcopenia (р=0.067).

In most participants (n=23, 63.9%), carotid atherosclerotic was reported (see Fig.). Approximately one-third of the enrolled individuals (n=13, 36.1%) had no signs of carotid atherosclerosis.

As to the pattern of carotid artery disorders (according to the RCRPC grading system) based on muscular system health, carotid atherosclerotic plaques were missing in three persons without sarcopenia (30.0%) but identified in three patients with presarcopenia (25.0%) and three patients with sarcopenia (21.4%). No significant differences in the rate of lacking atherosclerotic plaques were revealed between the groups (p>0.05).

A single atherosclerotic plaque with <50% stenosis was detected in two individuals in group 1 (20.0%), three patients in group 2 (25.0%), and two patients in group 3 (14.3%) Meanwhile, these differences were insignificant (p>0.05).

Multiple atherosclerotic plaques with <50% stenosis were detected in one individual without sarcopenia (10.0%), three patients with presarcopenia (25.0%), and one patient with sarcopenia (7.1%). Meanwhile, these differences were insignificant (p>0.05).

A single atherosclerotic plaque with ≥50% stenosis was detected in two individuals without sarcopenia (20.0%), one patient with presarcopenia (8.3%), and one patient with sarcopenia (7.1%). Meanwhile, these differences were insignificant (p>0.05).

Multiple atherosclerotic plaques with ≥50% stenosis were reported in patients with sarcopenia compared to patients with presarcopenia (35.7% vs. 8.3%, р=0.015) and persons without sarcopenia (35.7% vs. 10.0%, р=0.013). The rates of this variant of carotid atherosclerosis were similar in individuals without sarcopenia and patients with sarcopenia.

Despite the presence of carotid artery atherosclerotic plaques in all groups, the most severe carotid atherosclerosis (multiple atherosclerotic plaques, ≥50% stenosis) were more common in men with sarcopenia.

Correlation analysis revealed a reliable negative correlation between IMT and skeletal muscle area at the LIII level (r=-0.311, р=0.005) and IMT and skeletal muscle index (r=-0.282, p=0.012).

A similar correlation was revealed between IMT and right- and left-hand grip strength (r=-0.297, р=0.008 and r=-0.245, р=0.029, respectively). No significant correlations between IMT and muscle function were revealed (p>0.05).

To assess the effect of muscle system health parameters on IMT, stepwise regression method was applied. IMT was considered the main variable, while muscle mass, strength, and function were considered influencing variables.

We failed to interpret a model without parameter β reliability (testim<ttable) derived from linear regression analysis as a utility model.

Рисунок. Структура атеросклеротического поражения сонных артерий у обследованных пациентов (%) Figure. The structure of carotid atherosclerotic lesions in the examined patients (%)

Discussion

Despite the “youth” of secondary sarcopenia issue, many studies suggest a higher risk of myocardial infarction, atrial fibrillation, and aortic and coronary artery calcification in patients with sarcopenia [8, 10]. Quite a few studies, have established a more severe course of carotid [6, 8, 17, 18], coronary artery, and peripheral artery atherosclerosis [19, 20].

Thus, according to the Western Denmark Heart Registry with coronary atherosclerosis confirmed by coronary angiography, 15.6% patients died over 11 years of follow-up. Moreover, the risk of death was twice higher in underweight patients [21]. These findings support the view that in the elderly, body mass index is a marker of body protein reserves rather than obesity and directly affects muscle mass. Meta-analysis of 11 clinical trials by Y. Zhang et al. [22] reported a high prevalence of sarcopenia in patients with heart failure. Thus, the overall rate of this phenomenon varies from 10% to 69%, being detected in more than half of the patients in inpatient settings (55%, 95% CI 43%–66%) and a quarter of patients in outpatient settings (26%, 95% CI 16%–37%).

Our study has demonstrated that IMT is significantly higher in patients with sarcopenia than in individuals without sarcopenia. These findings agree with the study by J.E. Heo et al. [17] who examined 595 men and 1,274 women aged 30–64 and showed that carotid artery IMT significantly increased as appendicular lean mass reduced. A similar pattern was derived by M. Arnold et al. [6] and Y. Cao et al. [8] who demonstrated a significant correlation between muscle mass reduction and IMT increase, and M. Ochi et al. [18] who demonstrated a significant correlation between greater rigidity of the arterial wall and lower limb muscle mass.

The rates of atherosclerotic plaques in the carotid artery were naturally similar in the groups since atherosclerotic plaques are the basic course of stenosis, irrespective of muscle system health. However, the most severe carotid atherosclerosis has been reported in patients with sarcopenia. These findings agree with the study by M. Arnold et al. [6] who failed to identify any significant associations between the presence of atherosclerotic plaques and changes in muscle mass parameters, and the study by J.E. Heo et al. [17] who demonstrated that the rates of atherosclerotic plaques in the carotid arteries are similar in patients with low and normal muscle mass.

The inverse association between IMT and muscular strength parameters is of particular interest. Some evidence suggests that muscular strength is the earliest predictor of coronary atherosclerosis. Thus, X. Melo et al. [23] have examined 191 girls aged 11–12 and demonstrated that children with low muscular strength have significantly higher ITM and blood pressure, thereby illustrating an association between muscular strength and cardiovascular risk even in childhood. A similar pattern in elderly men was demonstrated in a prospective study by M.E. den Ouden et al. [24]. The authors conclude that low upper limb muscular strength at baseline is associated with a significant increase in IMT over a 4-year follow-up period. A study by H. Yamanashi et al. [11] in male patients produced similar results.

Conclusions

Therefore, an association between carotid atherosclerosis and abnormal body composition in men with knee OA allows to consider atherosclerosis and sarcopenia as two conditions, which share pathogenic mechanisms and potentially increase the risk of unfavorable outcomes. Future studies should focus on this association in various clinical variants of knee OA.


About the authors:

Lyudmila I. Alekseeva — Dr. Sc. (Med.), Head of the Department of Metabolic Bone and Joint Diseases, Research Institute of Rheumatology named after V.A. Nasonova; 34A, Kashirskoye road, Moscow, 115522, Russian Federation; Professor of the Department of Rheumatology, Russian Medical Academy of Continuous Professional Education; 2/1, Barrikadnaya str., Moscow, 125993, Russian Federation.

Elena A. Taskina — C. Sc. (Med.), Senior Researcher of the Department of Metabolic Bone and Joint Diseases, Research Institute of Rheumatology named after V.A. Nasonova; 34A, Kashirskoye road, Moscow, 115522, Russian Federation; ORCID iD 0000-0001-8218-3223.

Tatiana A. Raskina — Dr. Sc. (Med.), Professor, Head of the Department of Propaedeutics of Internal Diseases, Kemerovo State Medical University; 22A, Voroshilova str., Kemerovo, 650056, Russian Federation.

Marina V. Letaeva — C. Sc. (Med.), Associate Professor of the Department of Propaedeutics of Internal Diseases, Kemerovo State Medical University; 22A, Voroshilova str., Kemerovo, 650056, Russian Federation; ORCID iD 0000-0003-3907-7120.

Olga S. Malyshenko — C. Sc. (Med.), Associate Professor of the Department of Propaedeutics of Internal Diseases, Kemerovo State Medical University; 22A, Voroshilova str., Kemerovo, 650056, Russian Federation; ORCID iD 0000-0001-8272-3736.

Marina V. Koroleva — C. Sc. (Med.), Assistant of the Department of Propaedeutics of Internal Diseases, Kemerovo State Medical University; 22A, Voroshilova str., Kemerovo, 650056, Russian Federation; ORCID iD 0000-0002-0184-7997.

Yulia V. Averkieva — C. Sc. (Med.), Assistant of the Department of Propaedeutics of Internal Diseases, Kemerovo State Medical University; 22A, Voroshilova str., Kemerovo, 650056, Russian Federation; ORCID iD 0000-0001-8020-4545.

Inessa I. Grigorieva — rheumatologist, Kemerovo City Clinical Hospital No. 4; 12A, Bazovaya str., Kemerovo, 650024, Russian Federation.

Contact information: Marina V. Letaeva, e-mail: letaeva@yandex.ru.

Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.

There is no conflict of interests.

Received 02.03.2022.

Revised 29.03.2022.

Accepted 21.04.2022.

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