Background—: Atherosclerosis is considered to be an inflammatory disease associated with the activation of hematopoietic and immune-related organs such as the bone marrow (BM) and spleen. We evaluated the metabolic activity of those organs and of the carotid artery with ¹⁸ F-fluorodeoxyglucose positron emission tomography in patients with coronary artery disease, including acute myocardial infarction. Methods and Results—: Whole-body combined ¹⁸ F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 32 patients with acute myocardial infarction, 33 patients with chronic stable angina, and 25 control subjects. The mean standard uptake value was calculated in the regions of interest in the spleen and the BM of lumbar vertebrae. The target-to-background ratio of the standard uptake values of the carotid artery and jugular vein was also calculated. In patients with acute myocardial infarction, the standard uptake values of the BM (1.67±0.16) and spleen (2.57±0.39), as well as the target-to-background ratio of the carotid artery (2.13±0.42), were significantly higher than the corresponding values of patients with angina (1.22±0.62; 2.03±0.35; 1.36±0.37; all P <0.001) and controls (0.80±0.44; 1.54±0.26; 1.22±0.22; all P <0.001), independent of traditional cardiovascular risk factors and high-sensitivity C-reactive protein. In all groups combined, the target-to-background ratio of the carotid artery was significantly associated with the standard uptake values of the BM ( r =0.535; P <0.001), spleen ( r =0.663; P <0.001), and high-sensitivity C-reactive protein ( r =0.465; P <0.001). Conclusions—: The metabolic activity of the BM and spleen, as well as of the carotid artery, was highest in patients with acute myocardial infarction, intermediate in patients with angina, and lowest in control subjects. The activation of the BM and spleen was significantly associated with inflammatory activity of the carotid artery.

The impact of sarcopenia on atherosclerotic cardiovascular disease remains unclear. We aimed to investigate the prognostic impact of sarcopenia on coronary artery disease (CAD). A total of 475 patients with CAD who underwent successful percutaneous coronary intervention (PCI) and computed tomography (CT) were enrolled. The cross-sectional area of skeletal muscle at the first lumbar (L1) vertebral level was measured, and sex-specific cut-off values of L1 skeletal muscle index (L1 SMI; male <31.00 cm²/m², female <25.00 cm²/m²) were obtained. The primary outcome was 3-year all-cause mortality and the secondary outcome was 3-year major adverse cardiovascular events (MACEs). Low L1 SMI was present in 141 (29.7%) of 475 patients. The incidence of all-cause mortality (23.7% vs. 5.9%, p < 0.001) and MACEs (39.6% vs. 11.8%, p < 0.001) was significantly higher in patients with low L1 SMI than in those with high L1 SMI. In multivariate analysis, low L1 SMI was an independent predictor of higher risk of all-cause mortality (hazard ratio (HR): 4.07; 95% confidence interval (CI): 1.95–8.45; p < 0.001) and MACEs (HR: 3.76; 95% CI: 2.27–6.23; p < 0.001). These findings remained consistent after propensity score-matched analysis with 91 patient pairs (C-statistic = 0.848). CT-diagnosed low skeletal muscle mass is a powerful predictor of adverse outcomes in patients with CAD undergoing PCI.

Although triglyceride accumulation in the liver causes non-alcoholic fatty liver disease (NAFLD), hypercholesterolemia is also a main cause of NAFLD as well as atherosclerosis. However, NAFLD and atherosclerosis have not been investigated simultaneously in animal models fed a high-cholesterol diet. Moreover, it is unclear whether systemic inflammation can exacerbate both pathologies in the same model. Accordingly, this study investigated the effect of additional systemic inflammation on NAFLD and atherosclerosis induced by cholesterol overload in wild animals. New Zealand white rabbits were divided into 4 groups: groups I (control) and II received normal chow, and groups III and IV received a 1% cholesterol diet. To induce inflammation via toll-like receptor (TLR)-4 signaling, groups II and IV received subcutaneous injections of 0.5 mL of 1% carrageenan every 3 weeks. After 3 months, total cholesterol markedly increased in groups III and IV, and the serum expressions of systemic inflammatory markers were elevated in the groups II–IV. Early NAFLD lesions (e.g., mild fatty changes in the liver with sporadic fibrosis) and atherosclerosis (e.g., intimal hyperplasia composed of foam cells) were observed in both the liver and aorta specimens from group III, and advanced lesions were observed in group IV. The expressions of inflammatory cellular receptors, TLR-2 and TLR-4, in the aorta gradually increased from group I to IV but were similar in the liver in groups II–IV. Cholesteryl ester (CE) levels were higher in group IV than in group III, although the difference was not significant. CE levels in the aorta were similar between groups III and IV. Systemic inflammation can simultaneously exacerbate existing early lesions due to cholesterol overload in both the liver and aorta of rabbits. However, the cellular response of inflammatory receptors and expression of cholesterol metabolites differ between these organs.

Serum uric acid (UA) has been known to have a positive association with blood pressure (BP). However, the relationship between serum UA and BP in different age groups is unclear. A total of 45,098 Koreans who underwent health examinations at Korea Association of Health Promotion with no history of taking drugs related with UA and/or BP were analyzed for determining the relationship between serum UA and BP. In men <40, serum UA was significantly associated with systolic (β = 0.25, p = 0.002) and diastolic BP (β = 0.41, p < 0.001) after adjustment for age, diabetes, dyslipidemia, body mass index, and estimated glomerular filtration rate. Men between ages 40 and 59 showed similar results regarding diastolic BP. The association between serum UA and BP was stronger in women <40 (β = 0.54, p < 0.001 for systolic BP; β = 0.65, p < 0.001 for diastolic BP) and in between 40 and 59 (β = 0.51, p < 0.001 for diastolic BP). The association was not significant in men and women ≥60. The odds ratios (ORs) of hyperuricemia for hypertension were 1.25 (95% confidence interval [CI], 1.08 to 1.45; p = 0.003) and 1.33 (95% CI, 1.11 to 1.60; p = 0.002) in men <40 and in between 40 and 59, respectively, in the multivariate analysis. The OR was 2.60 (95% CI, 1.37 to 4.94; p = 0.0034) in women <40. The relationship between hyperuricemia and hypertension was not significant in other age/gender groups. In contrast to the elderly of 60 and over, the non-elderly showed significant associations between serum UA and BP.

Hyun-Hwa Son, Ju-Yeon Moon, Hong Seog Seo, Hyun Hee Kim, Bong Chul Chung, Man Ho Choi

Activated macrophages take up 2-deoxy-2-¹⁸F-fluoro-D-glucose (FDG) via glucose transporters, so this compound is useful for atherosclerosis imaging by positron emission tomography (PET). However, FDG application is limited for imaging of the heart and brain, where glucose uptake is high, and in patients with aberrant glucose metabolism. The aims of this study were to confirm that mannosylated human serum albumin (MSA) specifically binds to the mannose receptor (MR) on macrophages and to test the feasibility of ⁶⁸Ga-labeled NOTA-MSA for PET imaging of atherosclerotic plaques. Methods: The peritoneal macrophages of C57/B6 mice were collected, incubated with 10 μg/ml RITC-MSA, and evaluated by confocal microscopy and flow cytometry. The same evaluations were performed after pre-incubation of the macrophages with anti-CD206 MR blocking antibodies. NOTA-MSA was synthesized by conjugating 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid to MSA, followed by labeling with ⁶⁸Ga. Rabbits with atherosclerotic aorta induced by a 3-month cholesterol diet and chronic inflammation underwent consecutive PET/computed tomography with ¹⁸F-FDG and ⁶⁸Ga-NOTA-MSA at 2-day intervals. Results: The binding of MSA to MR, and its dose-dependent reduction by pre-incubation with anti-CD206 MR blocking antibody, were confirmed. Rhodamine B isothiocyanate (RITC) and fluorescein isothiocyanate (FITC) fluorescence co-localized at the atherosclerotic plaque. The ⁶⁸Ga-NOTA-MSA standard uptake values of the atherosclerotic aorta were significantly higher than those of the healthy arteries and inferior vena cava, and were comparable to those obtained with ¹⁸F-FDG. Conclusion: These findings suggest that MR-specific ⁶⁸Ga-NOTA-MSA is effective for detecting atherosclerosis in the aorta, and is a promising radiopharmaceutical for imaging atherosclerosis because of the presence of M2 macrophages in atherosclerotic plaques.