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Investigation on involvement of oxidative stress and glycosylation stress in patients with cardiovascular disease

Investigation on involvement of oxidative stress and glycosylation stress in patients with cardiovascular disease

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Cardiovascular disease (coronary artery disease, valvular disease, heart failure, arrhythmia, aortic disease, peripheral artery disease, cerebrovascular disease). It has become clear that it accelerates the glycation reaction and causes vascular disorders. We will noninvasively measure the degree of oxidative stress and glycative stress, and examine their roles in the onset and progression of cardiovascular diseases. From February 15, 2019 to January 2023, 97 cardiovascular disease patients were enrolled, which became a specified clinical study under the transitional measures mentioned above. The purpose of this study was to investigate the relationship between oxidative stress and glycative stress in patients with cardiovascular disease. To investigate cardiovascular events (acute coronary syndrome, revascularization, heart failure, stroke, and other hospitalizations) and death and to examine their associations. It is stipulated that the prognosis will be investigated one year after the examination and three years after the examination starting from the examination date, and 73 subjects whose AGEs can be measured and whose prognosis can be investigated before the end of the study. An analysis was performed (median age 67 years, 56 males 77%). The remaining 24 subjects were excluded from the study because the prognosis survey was conducted after the end of the study period.

A total of 97 patients were registered, including 73 in 2019, 10 in 2020, 11 in 2021, and 3 in 2022. Of the total, 55% had post-open-heart surgery, 25% had chronic heart failure, 18% had coronary artery disease, and 2% had other cardiovascular disease.

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In the study protocol, unless otherwise specified, the significance level is set to 5% on both sides and the confidence coefficient is set to 95% on both sides. The study subject background is calculated by calculating the mean and standard deviation for continuous variables, and by calculating the frequency and ratio for categorical variables. If a continuous variable clearly does not follow a normal distribution, transform the variable appropriately, such as by logarithmic transformation, and aggregate the mean and standard deviation, or use the median and interquartile range as descriptive statistics. For the primary endpoint, between-group comparisons will be performed with baseline as a covariate, analysis of covariance will be performed, and adjusted mean values, their 95% confidence intervals, and p-values will be calculated. Within group comparisons are performed by paired t-test. For safety, the frequency and ratio are calculated for each group and for each item, and comparisons between groups are performed using Fisher's exact test. However, since the primary analysis method described in the research protocol did not correspond to the primary endpoint and the analysis was not feasible, analysis was performed using a method not described in the research protocol did The results are described below. Concerning the measurement of urinary 8-OHdG, it became difficult to carry out the measurement due to funding issues, and it was difficult to consider oxidative stress. Simultaneous measurement of skin and subcutaneous AGEs on the forearms and fingertips of the entire subject was performed. The median value is used as the statistic due to the non-normal distribution for AGEs. In order to examine the correlation between the two, the correlation coefficient was calculated by covariance analysis of bivariate analysis. AGEs (forearm measurement) was 2.64 (median quartile 2.25-2.9) and AGEs (fingertip measurement) was 0.54 (median quartile 0.4-0.62). No significant correlation was found between the two. A prognostic survey was conducted until January 9, 2023, with a major cardiovascular event as the endpoint, and a survival analysis was performed. During a median follow-up period of 1077 days, 18 (24%) patients had an event. In order to examine cardiovascular events associated with glycative stress, we divided patients into two groups based on the presence or absence of events, and compared patient backgrounds and clinical data. In the event group, there was no significant difference in patient background, and AGEs were significantly higher (2.85 vs. 2.57 P=0.03). We divided the two groups according to the median value of AGEs and compared the event rates, but no significant difference was observed. Measurement of skin and subcutaneous AGEs was easy and safe. Forearm-measured AGEs values were significantly higher in the event group. In addition, analysis of the secondary endpoints of endothelial function and change in HbA1c was difficult due to differences in the study protocol and the patient's informed consent form.

Measurement of skin and subcutaneous AGEs was easy and safe. Forearm-measured AGEs values were significantly higher in the event group. In addition, analysis of the secondary endpoints of endothelial function and change in HbA1c was difficult due to differences in the study protocol and the patient's informed consent form.

Feb. 06, 2023

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs032180156

Yokoyama Miho

Juntendo University Hospital

3-1-3 Hongo,Bunkyo-ku,Tokyo

mipocch@juntendo.ac.jp

Yokoyama Miho

Juntendo University

2-1-1Hongo,Bunkyo-ku,Tokyo

+81-3-3813-3111

mipocch@juntendo.ac.jp

Complete

Mar. 16, 2018

Interventional

single arm study

open(masking not used)

no treatment control/standard of care control

single assignment

prevention purpose

1.Coronary artery disease
2.Valvular disease
3.Heart failure
4.Arrhythmia
5.Aortic disease
6.Peripheral arterial disease
7.Cerebrovascular disease
8.Men and women over 20 years old
9.One who gained document consent by free will of the research subject after having sufficient explanation for participation in this research, with sufficient understanding.

1.Patients with severe complications (problems with extremity cutting, severe skin complications)
2.Other who judged that the research director is inappropriate as the research subject

Both

Cardiovascular diseases

Measurement with unapproved medical equipment

Major cardiovascular events (acute coronary syndrome, revascularization surgery, heart failure, stroke, other hospitalization) and death

Body composition, endothelial function, HbA1c change amount

+81-3-5802-1584

Feb. 05, 2019

none