Prediction Of Cerebrovascular/cardiovascular Disease Secondary To Metabolic Syndrome: Ultrasonographic Measures Of Vasodilator Response Ⅱ

Discussion

The FMD/NID measurements were examined by ultrasonography to determine their functional utility as surrogate markers for the early prediction of CCVD which occurred frequently during the clinical follow-up period of CKD pathophysiologically based on MetS. There were 208 subjects evaluated for the incidence of CCVD (Figure 1). The incidence of CCVD increased with a decrease in eGFR, an index of renal function in CKD, as shown by 22.2%, 17.3%, 25.5%, 30.4%, 60.0%, and 75.0% at eGFR levels of G1, G2, G3a, G3b, G4, and G5, respectively. According to the results obtained, subjects with CCVD were already present at the eGFR level of G1 to G2, and the incidence of CCVD increased with worsening impairment of renal function thereafter. These findings were reviewed for the effectiveness of FMD/NID as surrogate markers for the prediction of CCVD affecting the subject's vital prognosis and loss of quality of life. The results are discussed in the following sections.

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1. FMD

Maruhashi et al. reported that 7277 Japanese subjects had FMD values of 7.5% ± 3.3% (median, 7.3%; interquartile range, 5.3-9.4%) in the no-risk group and 5.9 ± 2.9% (median, 5.7%; interquartile range, 3.9-7.5%) in the risk group10). The mean FMD value for G-T was significantly lower than the FMD cutoff value. Furthermore, the mean FMD value was lower in G-A than in G-B and G-C than in G-D, although the difference between the two subject groups was not significant (Figures 2 and 3). In other words, FMD had significantly lower values (as compared to the cutoff value) in general, without resulting in the detection of CCVD or an increasing number of MetS risk factors. This finding suggests that, in the early stage of MetS, FMD values are already low, and atherosclerotic lesions have already occurred. 

2. NID 

Maruhashi et al.10) reported that 1764 Japanese subjects had NID values of 17.7 ± 5.7% (median, 17.4%; interquartile range, 13.2-21.7%) in the no-risk group and 11.7 ± 5.9% (median, 11.4%; interquartile range, 7.4-13.5%) in the risk group. The mean NID value for G-T was significantly lower than the NID cutoff value, in G-A than in G-B, and in G-C than in G-D (Figures 4 and 5). These findings suggest that atherosclerotic lesions degenerate with an increasing number of MetS risk factors present, thereby causing CCVD. FMD (an indicator of vascular endothelial cell dysfunction) and NID (an indicator of medial smooth muscle layer hypofunction) values were assessed in the target subjects didiagnosed with MetS by taking into consideration the cutoff values (FMD, 7.1%; NID, 15.6%) defined in a previous study. At the time of assessment, abnormally low levels of FMD were observed in 93.8% of the subjects, whereas the levels of NID remained at 66.8%. Incidentally, when the FMD cutoff value of 4.0% was used, low levels of FMD were found in 69.3% of the subjects. Meanwhile, when the NID cutoff value of 15.1% was used, low levels of NID were found in 60% of the subjects. If intimal and medial functions are assumed to be similar in the degree of deterioration, the adoption of an FMD cutoff value of 4.0% might be correct. The FMD and NID data were then analyzed from the standpoint of the presence or absence of CCVD and the number of MetS risk factors. The FMD whose values were low in all target subjects showed no difference between the presence and absence of CCVD (G-A and G-B) or between 4 and 3 risk factors for MetS (G-C and G-D), whereas the NID whose values were not low in many subjects, showed a significant difference about the presence or absence of CCVD and the number of MetS risk factors. These results suggest that the decrease in the FMD value in subjects with MetS might precede that of the NID value. This also suggests that FMD may be useful in arteriosclerosis-based diagnostic screening for CCVD while definitive diagnosis can be facilitated by NID. These findings show that individuals diagnosed with MetS in their recent medical check-ups in Japan in 2008 should actively undergo ultrasonographic examination for RI/eRBF in the case of CKD and FMD/NID in the case of CCVD to consider for early diagnosis and proper treatment. This is expected to prevent the development and progression of these diseases.

Conclusion 

Concerning the early diagnosis of CKD, it has already been reported that RI and eRBF, as measured by ultrasonography, are useful and important predictors of CKD pathophysiologically based on MetS. Furthermore, confidently, given the findings that the decrease in the FMD value in target subjects indicated the onset of arteriosclerotic lesions and that the decrease in the NID value was associated with the progression of arteriosclerosis, FMD/NID measurements by ultrasonography demonstrate that it serves to be a useful significant surrogate marker for the early predictive/definite diagnosis of CCVD. In summary, FMD and NID are important measurement parameters as predictors/determinants of CCVD, which occur frequently as the pathophysiological basis of MetS during the progression of renal damage leading to end-stage renal failure. In conclusion, the findings suggest that the RI and eRBF measurements and FMD and NID measurements by ultrasonography may be utilized as an accurate diagnostic tool for the early diagnosis of CKD and CCVD as arterioleerotic organopathies occurring based on MetS. Thus, early comprehensive diagnosis of CKD and CCVD will produce a beneficial effect on their prevention and treatment. AAcknowledgmentsWe would like to thank Dr. Yasumi Uchida and Dr. NaoTake Hashimoto for their careful guidance in writing the manuscript and tr. Toshio Hiroi for his kind assistance in translating it into English. Conflicts of Interest The authors have no financial conflicts of interest to disclose concerning this study. 

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