Endothelial dysfunction is one of the initial steps in the pathogenesis of atherosclerosis and development of cardiovascular disease in patients with diabetes mellitus. Several risk factors are associated with endothelial dysfunction and atherosclerosis, such as hypertension, dyslipidaemia, inflammation, oxidative stress, and advanced glycation-end products. Among these risk factors, oxidative stress is the largest contributor to the formation of atherosclerotic plaques. Measurement of reactive oxygen species (ROS) is still difficult, and assays for the measurement of ROS have failed to show a consistent correlation between pathological states and oxidative stress. To solve this problem, this review summarizes the current knowledge on biomarkers of oxidative stress, especially lipid peroxidation, and discusses the roles of oxidative stress, as measured by indices of lipid peroxidation, in diabetes mellitus, atherosclerosis, and chronic inflammation.

Lipid markers are well-established predictors of vascular disease. The most frequently measured lipid markers are total cholesterol, high-density lipoprotein (HDL)-cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglyceride. HDL reduces atherosclerosis by multiple mechanisms, leading to a reduced risk of cardiovascular disease, and HDL-C, as a metric of HDL quantity, is inversely associated with cardiovascular disease, independent of LDL-C. However, the quality of the HDL appears to be more important than its quantity, because HDL loses its antiatherogenic functions due to changes in its composition and becomes “dysfunctional HDL”. Although there is evidence of the existence of “dysfunctional HDL”, biomarkers for monitoring dysfunctional HDL in clinical practice have not yet been established. In this review, we propose a new lipid panel for the assessment of dysfunctional HDL and lipoprotein-related atherosclerotic cardiovascular disease. The lipid panel includes the measurement of lipid peroxide and triglyceride contents within HDL particles.

Reactive oxygen species (ROS) are involved in the initiation and progression of atherosclerosis. ROS-derived hydroperoxides, as an indicator of ROS production, have been measured by using the diacron reactive oxygen metabolites (d-ROMs) test, which requires iron-containing transferrin in the reaction mixture. In this study we developed a modified d-ROMs test, termed the Fe-ROMs test, where iron ions were exogenously added to the reaction mixture. This modification is expected to exclude the assay variation that comes from different blood iron levels in individuals. In addition, this Fe-ROMs test was helpful for determining the class of plasma lipoproteins that are hydroperoxidized. Low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and high-density lipoprotein (HDL) were purified by use of an LDL/VLDL purification kit and the dextran sulfate-Mg²⁺ precipitation method, respectively; their hydroperoxide contents were assessed by performing the Fe-ROMs test. The majority of the hydroperoxides were detected only in the HDL fraction, not in the LDL/VLDL. Further detailed analysis of HDLs by size-exclusion high-performance liquid chromatography revealed that the hydroperoxide-containing molecules were small-sized HDLs. Because HDL was shown to be the principal vehicle for the plasma hydroperoxides, this Fe-ROMs test is a beneficial method for the assessment of oxidized-HDL levels. Indeed, Fe-ROMs levels were strongly associated with the levels of oxidized HDL, which were determined by performing the malondialdehyde-modified HDL enzyme immunoassay. In conclusion, the Fe-ROMs test using plasma itself or the HDL fraction after dextran sulfate-Mg²⁺ precipitation is useful to assess the functionality of HDL, because the oxidation of HDL impairs its antiatherogenic capacity.

Cardiopulmonary function is usually assessed by cardiopulmonary exercise testing (CPX) using a cycle ergometer (CE-CPX) or a treadmill, which is difficult in patients with lower extremity motor dysfunction. A stepping and handshaking (SHS) exercise has been developed that can be performed safely and easily while sitting on a chair. This study compared peak oxygen uptake (peak $\stackrel{.}{\mathrm{V}}{\mathrm{O}}_2$) between CE-CPX and SHS-CPX in healthy adults and investigated the safety and validity of SHS-CPX. Twenty young adults (mean age 27.8 ± 4.4 years) were randomly assigned to perform CE-CPX or SHS-CPX, with the other test to follow 1–2 weeks later. The peak $\stackrel{.}{\mathrm{V}}{\mathrm{O}}_2$, respiratory exchange ratio (RER), peak heart rate, blood pressure, and test completion time were compared between CE-CPX and SHS-CPX. All subjects completed the examination and met the criteria for peak $\stackrel{.}{\mathrm{V}}{\mathrm{O}}_2$. SHS-CPX and CE-CPX showed a strong correlation with peak $\stackrel{.}{\mathrm{V}}{\mathrm{O}}_2$ (r = 0.85, p < 0.0001). The peak $\stackrel{.}{\mathrm{V}}{\mathrm{O}}_2$ (40.4 ± 11.3 mL/min/kg vs. 28.9 ± 8.0 mL/min/kg), peak heart rate (190.6 ± 8.9 bpm vs. 172.1 ± 12.6 bpm), and test completion time (1052.8 ± 143.7 s vs. 609.1 ± 96.2 s) were significantly lower in the SHS-CPX (p < 0.0001). There were no adverse events. The peak $\stackrel{.}{\mathrm{V}}{\mathrm{O}}_2$ with SHS-CPX was equivalent to about 70% of that with CE-CPX despite the exercise being performed in a sitting position, suggesting its suitability as a submaximal exercise test.

Patients with cervical spinal cord injuries (CSCI) experience hypotension mainly caused by attenuated total peripheral resistance. Some physicians and nurses believe that this peripheral blood pressure (PBP) decrease in patients with CSCI results in the formation of pressure injuries. We hypothesized that the measurement of PBP, such as arteriole and capillary pressure, could be a simple and efficient means of detecting skin and deep tissue damage in patients with CSCI. However, PBP in the skin has not been measured in patients with CSCI. The purpose of this study was to investigate PBP in patients with CSCI. Eleven men patients with CSCI with a lesion between C6 and C7 (American Spinal Injury Association score A, average age 32.5 years) and 13 healthy participants (average age 40.1 years) participated in the study. To measure PBP, laser Doppler blood flowmetry with a fixed pressure transducer was gently applied to the pretibial skin, and the pressure when skin blood velocity was zero was determined as the PBP. The mean blood pressure (MBP) was measured simultaneously. There was a significant correlation between MBP and PBP in patients with CSCI, but not in healthy individuals. A significantly lower MBP was observed in patients with CSCI (means ± SE; 76.7 ± 3.9 mm Hg) than in healthy individuals (means ± SE; 91.0 ± 4.0 mm Hg). PBP in patients with CSCI (means ± SE; 55.7 ± 2.0 mm Hg) was significantly greater than in healthy individuals (means ± SE; 45.9 ± 2.3 mm Hg). Transection of the sympathetic nervous system from the medulla to the peripheral nerves in patients with CSCI results in decreased MBP and increased PBP. We suggest that cervical spine transection diminishes the tonic impulses of sympathetic nerves to resistant vessels in patients with CSCI.