Response to “Associations Among Plasma Total Homocysteine Levels, Circadian Blood Pressure Variation, and Endothelial Function in Hypertension”

Response to “Associations Among Plasma Total Homocysteine Levels, Circadian Blood Pressure... To the Editor: We thank Dr Tsuda for his interest1 in our recent article “Plasma Homocysteine Levels Are Associated With Circadian Blood Pressure Variation in Chinese Hypertensive Adults.”2 Dr Tsuda is interested in whether endothelial function might be related to plasma total homocysteine (tHcy) levels, 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and circadian blood pressure variation in the study. In order to answer this question, we matched 390 hypertensive patients who received peripheral endothelial function assessment by Endo-PAT2000 device (Itamar Medical, Caesarea, Israel).3 Patients were from a different cohort. These patients also underwent ambulatory BP monitoring and tHcy level measurements at the same time. Digital reactive hyperemia peripheral arterial tonometry (RH-PAT) index computed automatically by Endo-PAT2000 software was used to represent the endothelial function in study, as described by us previously.3 An RH-PAT index ≤1.67 was considered abnormal. Unfortunately, we could not collect enough data about MTHFR polymorphism in this cohort. Pearson’s correlation was used for simple linear analysis between ln(RH-PAT) and ln(tHcy). We did not find a significant correlation between ln(RH-PAT) and ln(tHcy) in all patients (r = −0.089, P = 0.081). However, a significant correlation between ln(RH-PAT) and ln(tHcy) was found in female patients (Figure 1a) but not in male patients (Figure 1b) which was consistent with our previous report.4 Compared with nondippers, there was a tendency of higher RH-PAT index in dippers although there was no significant difference between these 2 groups (Figure 2). Analysis further revealed that there was no significant correlation between ln(nocturnal systolic blood pressure fall) and ln(RH-PAT) in all patients (Figure 3a). However, there was a significant correlation between ln(nocturnal diastolic blood pressure fall) and ln(RH-PAT) (Figure 3b), indicating better peripheral endothelial function in patients with greater reductions of nocturnal diastolic blood pressure. Figure 1. View largeDownload slide Simple linear analysis between ln(RH-PAT) and ln(tHcy) in male patients (a) and female patients (b). Abbreviations: Ln, natural logarithm; RH-PAT, digital reactive hyperemia peripheral arterial tonometry; tHcy, total homocysteine. Figure 1. View largeDownload slide Simple linear analysis between ln(RH-PAT) and ln(tHcy) in male patients (a) and female patients (b). Abbreviations: Ln, natural logarithm; RH-PAT, digital reactive hyperemia peripheral arterial tonometry; tHcy, total homocysteine. Figure 2. View largeDownload slide RH-PAT index in dippers and nondippers. Data were not adjusted for confounders. Abbreviation: RH-PAT, digital reactive hyperemia peripheral arterial tonometry. Figure 2. View largeDownload slide RH-PAT index in dippers and nondippers. Data were not adjusted for confounders. Abbreviation: RH-PAT, digital reactive hyperemia peripheral arterial tonometry. Figure 3. View largeDownload slide Simple linear analysis between ln(RH-PAT) and ln(nocturnal SBP fall) (a) or ln(nocturnal DBP fall) (b), respectively, in all patients. Abbreviations: DBP, diastolic blood pressure; Ln, natural logarithm; RH-PAT, digital reactive hyperemia peripheral arterial tonometry; SBP, systolic blood pressure. Figure 3. View largeDownload slide Simple linear analysis between ln(RH-PAT) and ln(nocturnal SBP fall) (a) or ln(nocturnal DBP fall) (b), respectively, in all patients. Abbreviations: DBP, diastolic blood pressure; Ln, natural logarithm; RH-PAT, digital reactive hyperemia peripheral arterial tonometry; SBP, systolic blood pressure. The above preliminary results should be interpreted cautiously: (i) causal relationship between peripheral endothelial function and tHcy/nocturnal diastolic blood pressure fall could not be supported by cross-sectional study, (ii) endothelial function assessment would be affected by medication significantly, (iii) different estimation method for endothelial function might lead to discrepancy of data, (iv) we investigated only a relatively small number of patients from a single center, (v) menopausal status was not determined in female patients, and (vi) the statistical results were not corrected for cofounding factors. Nevertheless, as mentioned by Dr Tsuda, the current data have indicated an important relationship among tHcy, circadian blood pressure variation, and endothelial function in hypertension. We look forward to more research focusing on this relationship in hypertension. FUNDING This work was supported by a grant from National Natural Science Foundation of China (Grant no. 81460071); and Jiangxi “5511” Scientific and Technological Innovation Talent Project (Grant no. 20165BCB18020). DISCLOSURE The authors declared no conflict of interest. REFERENCES 1. Tsuda K. Associations among plasma total homocysteine levels, circadian blood pressure variation and endothelial function in hypertension. Am J Hypertens  2018; doi: 10.1093/ajh/hpy002. 2. Dong YF, Zhan BM, Hao QY, Ruan ZH, Xu ZX, Deng M, Chen DW, Zou YQ, Chen J, Li P, Cheng XS. Plasma homocysteine levels are associated with circadian blood pressure variation in Chinese hypertensive adults. Am J Hypertens  2017; 30: 1203– 1210. Google Scholar CrossRef Search ADS PubMed  3. Cao C, Hu JX, Dong YF, Zhan R, Li P, Su H, Peng Q, Wu T, Huang X, Sun WH, Wu QH, Cheng XS. Association of endothelial and mild renal dysfunction with the severity of left ventricular hypertrophy in hypertensive patients. Am J Hypertens  2016; 29: 501– 508. Google Scholar CrossRef Search ADS PubMed  4. Cao C, Hu J, Dong Y, Zhan R, Li P, Su H, Peng Q, Wu T, Lei L, Huang X, Wu Q, Cheng X. Gender differences in the risk factors for endothelial dysfunction in Chinese hypertensive patients: homocysteine is an independent risk factor in females. PLoS One  2015; 10: e0118686. Google Scholar CrossRef Search ADS PubMed  © American Journal of Hypertension, Ltd 2018. All rights reserved. For Permissions, please email: journals.permissions@oup.com http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Hypertension Oxford University Press

Response to “Associations Among Plasma Total Homocysteine Levels, Circadian Blood Pressure Variation, and Endothelial Function in Hypertension”

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Oxford University Press
Copyright
© American Journal of Hypertension, Ltd 2018. All rights reserved. For Permissions, please email: journals.permissions@oup.com
ISSN
0895-7061
eISSN
1941-7225
D.O.I.
10.1093/ajh/hpy015
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Abstract

To the Editor: We thank Dr Tsuda for his interest1 in our recent article “Plasma Homocysteine Levels Are Associated With Circadian Blood Pressure Variation in Chinese Hypertensive Adults.”2 Dr Tsuda is interested in whether endothelial function might be related to plasma total homocysteine (tHcy) levels, 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and circadian blood pressure variation in the study. In order to answer this question, we matched 390 hypertensive patients who received peripheral endothelial function assessment by Endo-PAT2000 device (Itamar Medical, Caesarea, Israel).3 Patients were from a different cohort. These patients also underwent ambulatory BP monitoring and tHcy level measurements at the same time. Digital reactive hyperemia peripheral arterial tonometry (RH-PAT) index computed automatically by Endo-PAT2000 software was used to represent the endothelial function in study, as described by us previously.3 An RH-PAT index ≤1.67 was considered abnormal. Unfortunately, we could not collect enough data about MTHFR polymorphism in this cohort. Pearson’s correlation was used for simple linear analysis between ln(RH-PAT) and ln(tHcy). We did not find a significant correlation between ln(RH-PAT) and ln(tHcy) in all patients (r = −0.089, P = 0.081). However, a significant correlation between ln(RH-PAT) and ln(tHcy) was found in female patients (Figure 1a) but not in male patients (Figure 1b) which was consistent with our previous report.4 Compared with nondippers, there was a tendency of higher RH-PAT index in dippers although there was no significant difference between these 2 groups (Figure 2). Analysis further revealed that there was no significant correlation between ln(nocturnal systolic blood pressure fall) and ln(RH-PAT) in all patients (Figure 3a). However, there was a significant correlation between ln(nocturnal diastolic blood pressure fall) and ln(RH-PAT) (Figure 3b), indicating better peripheral endothelial function in patients with greater reductions of nocturnal diastolic blood pressure. Figure 1. View largeDownload slide Simple linear analysis between ln(RH-PAT) and ln(tHcy) in male patients (a) and female patients (b). Abbreviations: Ln, natural logarithm; RH-PAT, digital reactive hyperemia peripheral arterial tonometry; tHcy, total homocysteine. Figure 1. View largeDownload slide Simple linear analysis between ln(RH-PAT) and ln(tHcy) in male patients (a) and female patients (b). Abbreviations: Ln, natural logarithm; RH-PAT, digital reactive hyperemia peripheral arterial tonometry; tHcy, total homocysteine. Figure 2. View largeDownload slide RH-PAT index in dippers and nondippers. Data were not adjusted for confounders. Abbreviation: RH-PAT, digital reactive hyperemia peripheral arterial tonometry. Figure 2. View largeDownload slide RH-PAT index in dippers and nondippers. Data were not adjusted for confounders. Abbreviation: RH-PAT, digital reactive hyperemia peripheral arterial tonometry. Figure 3. View largeDownload slide Simple linear analysis between ln(RH-PAT) and ln(nocturnal SBP fall) (a) or ln(nocturnal DBP fall) (b), respectively, in all patients. Abbreviations: DBP, diastolic blood pressure; Ln, natural logarithm; RH-PAT, digital reactive hyperemia peripheral arterial tonometry; SBP, systolic blood pressure. Figure 3. View largeDownload slide Simple linear analysis between ln(RH-PAT) and ln(nocturnal SBP fall) (a) or ln(nocturnal DBP fall) (b), respectively, in all patients. Abbreviations: DBP, diastolic blood pressure; Ln, natural logarithm; RH-PAT, digital reactive hyperemia peripheral arterial tonometry; SBP, systolic blood pressure. The above preliminary results should be interpreted cautiously: (i) causal relationship between peripheral endothelial function and tHcy/nocturnal diastolic blood pressure fall could not be supported by cross-sectional study, (ii) endothelial function assessment would be affected by medication significantly, (iii) different estimation method for endothelial function might lead to discrepancy of data, (iv) we investigated only a relatively small number of patients from a single center, (v) menopausal status was not determined in female patients, and (vi) the statistical results were not corrected for cofounding factors. Nevertheless, as mentioned by Dr Tsuda, the current data have indicated an important relationship among tHcy, circadian blood pressure variation, and endothelial function in hypertension. We look forward to more research focusing on this relationship in hypertension. FUNDING This work was supported by a grant from National Natural Science Foundation of China (Grant no. 81460071); and Jiangxi “5511” Scientific and Technological Innovation Talent Project (Grant no. 20165BCB18020). DISCLOSURE The authors declared no conflict of interest. REFERENCES 1. Tsuda K. Associations among plasma total homocysteine levels, circadian blood pressure variation and endothelial function in hypertension. Am J Hypertens  2018; doi: 10.1093/ajh/hpy002. 2. Dong YF, Zhan BM, Hao QY, Ruan ZH, Xu ZX, Deng M, Chen DW, Zou YQ, Chen J, Li P, Cheng XS. Plasma homocysteine levels are associated with circadian blood pressure variation in Chinese hypertensive adults. Am J Hypertens  2017; 30: 1203– 1210. Google Scholar CrossRef Search ADS PubMed  3. Cao C, Hu JX, Dong YF, Zhan R, Li P, Su H, Peng Q, Wu T, Huang X, Sun WH, Wu QH, Cheng XS. Association of endothelial and mild renal dysfunction with the severity of left ventricular hypertrophy in hypertensive patients. Am J Hypertens  2016; 29: 501– 508. Google Scholar CrossRef Search ADS PubMed  4. Cao C, Hu J, Dong Y, Zhan R, Li P, Su H, Peng Q, Wu T, Lei L, Huang X, Wu Q, Cheng X. Gender differences in the risk factors for endothelial dysfunction in Chinese hypertensive patients: homocysteine is an independent risk factor in females. PLoS One  2015; 10: e0118686. Google Scholar CrossRef Search ADS PubMed  © American Journal of Hypertension, Ltd 2018. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Journal

American Journal of HypertensionOxford University Press

Published: Apr 1, 2018

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