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Isolated diastolic hypertension is not associated with endothelial dysfunction

Hypertension Research volume 45, pages 698–707 (2022)Cite this article

Abstract

Hypertension is associated with an impairment of endothelial function. However, it is unclear whether isolated diastolic hypertension is associated with endothelial dysfunction. The purpose of this study was to investigate the association of endothelial function with isolated diastolic hypertension diagnosed by using two major hypertension guidelines: systolic blood pressure (BP) < 130 mmHg and diastolic BP ≥ 80 mmHg according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline and systolic BP < 140 mmHg and diastolic BP ≥ 90 mmHg according to the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) hypertension guideline. We measured the flow-mediated vasodilation (FMD) of the brachial artery in subjects without systolic hypertension who were not treated with antihypertensive drugs. Of 3727 subjects (2813 men; mean age: 41.3 ± 10.9 years), 749 (20.1%) had isolated diastolic hypertension according to the 2017 ACC/AHA definition. Multiple logistic regression analysis revealed that isolated diastolic hypertension was not associated with endothelial dysfunction, defined as FMD < 7.0% (OR, 1.15; 95% CI, 0.98–1.35; P = 0.09). Of 4747 subjects (3727 men; mean age: 45.1 ± 10.8 years), 314 subjects (6.6%) had isolated diastolic hypertension according to the ESC/ESH definition. Multiple logistic regression analysis revealed that isolated diastolic hypertension was not associated with endothelial dysfunction after adjusting for age and sex (OR, 1.04; 95% CI, 0.82–1.32; P = 0.76). Isolated diastolic hypertension was not associated with endothelial dysfunction in individuals who were not treated with antihypertensive drugs regardless of the major hypertension guideline definition used.

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References

  1. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies C. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13.

    Article  Google Scholar 

  2. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13–e115.

    CAS  PubMed  Google Scholar 

  3. McEvoy JW, Daya N, Rahman F, Hoogeveen RC, Blumenthal RS, Shah AM, et al. Association of isolated diastolic hypertension as defined by the 2017 ACC/AHA blood pressure guideline with incident cardiovascular outcomes. JAMA. 2020;323:329–38.

    Article  Google Scholar 

  4. Lee H, Yano Y, Cho SMJ, Park JH, Park S, Lloyd-Jones DM, et al. Cardiovascular risk of isolated systolic or diastolic hypertension in young adults. Circulation. 2020;141:1778–86.

    Article  Google Scholar 

  5. McGrath BP, Kundu P, Daya N, Coresh J, Selvin E, McEvoy JW, et al. Isolated diastolic hypertension in the UK biobank: comparison of ACC/AHA and ESC/NICE guideline definitions. Hypertension. 2020;76:699–706.

    Article  CAS  Google Scholar 

  6. Jacobsen AP, Al Rifai M, Arps K, Whelton SP, Budoff MJ, Nasir K, et al. A cohort study and meta-analysis of isolated diastolic hypertension: searching for a threshold to guide treatment. Eur Heart J. 2021;42:2119–29.

    Article  CAS  Google Scholar 

  7. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115–26.

    Article  CAS  Google Scholar 

  8. Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and oxidative stress in cardiovascular diseases. Circ J. 2009;73:411–8.

    Article  CAS  Google Scholar 

  9. Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation. 2005;111:363–8.

    Article  Google Scholar 

  10. Matsuzawa Y, Kwon TG, Lennon RJ, Lerman LO, Lerman A. Prognostic value of flow-mediated vasodilation in brachial artery and fingertip artery for cardiovascular events: a systematic review and meta-analysis. J Am Heart Assoc. 2015;4:e002270.

  11. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111–5.

    Article  CAS  Google Scholar 

  12. Benjamin EJ, Larson MG, Keyes MJ, Mitchell GF, Vasan RS, Keaney JF Jr, et al. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation. 2004;109:613–9.

    Article  Google Scholar 

  13. Yeboah J, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, et al. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation. 2009;120:502–9.

    Article  Google Scholar 

  14. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, et al. Endothelial dysfunction, increased arterial stiffness, and cardiovascular risk prediction in patients with coronary artery disease: FMD-J (Flow-Mediated Dilation Japan) study A. J Am Heart Assoc. 2018;7:e008588.

  15. Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323:22–7.

    Article  CAS  Google Scholar 

  16. Iiyama K, Nagano M, Yo Y, Nagano N, Kamide K, Higaki J, et al. Impaired endothelial function with essential hypertension assessed by ultrasonography. Am Heart J. 1996;132:779–82.

    Article  CAS  Google Scholar 

  17. Maruhashi T, Nakashima A, Kishimoto S, Iwamoto A, Kajikawa M, Oda N, et al. Reduction in blood pressure improves impaired nitroglycerine-induced vasodilation in patients with essential hypertension. Hypertens Res. 2015;38:862–8.

    Article  CAS  Google Scholar 

  18. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. ESC/ESH guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018;36:1953–2041. 2018.

    Article  CAS  Google Scholar 

  19. Tomiyama H, Kohro T, Higashi Y, Takase B, Suzuki T, Ishizu T, et al. A multicenter study design to assess the clinical usefulness of semi-automatic measurement of flow-mediated vasodilatation of the brachial artery. Int Heart J. 2012;53:170–5.

    Article  Google Scholar 

  20. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, et al. Hyperbilirubinemia, augmentation of endothelial function, and decrease in oxidative stress in Gilbert syndrome. Circulation. 2012;126:598–603.

    Article  CAS  Google Scholar 

  21. Tomiyama H, Kohro T, Higashi Y, Takase B, Suzuki T, Ishizu T, et al. Reliability of measurement of endothelial function across multiple institutions and establishment of reference values in Japanese. Atherosclerosis. 2015;242:433–42.

    Article  CAS  Google Scholar 

  22. Maruhashi T, Kajikawa M, Kishimoto S, Hashimoto H, Takaeko Y, Yamaji T, et al. Diagnostic criteria of flow-mediated vasodilation for normal endothelial function and nitroglycerin-induced vasodilation for normal vascular smooth muscle function of the brachial artery. J Am Heart Assoc. 2020;9:e013915.

    PubMed  PubMed Central  Google Scholar 

  23. Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, et al. The Japanese Society of Hypertension Guidelines for the management of hypertension (JSH 2019). Hypertens Res. 2019;42:1235–481.

    Article  Google Scholar 

  24. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39:257–65.

    Article  Google Scholar 

  25. Tomiyama H, Higashi Y, Takase B, Node K, Sata M, Inoue T, et al. Relationships among hyperuricemia, metabolic syndrome, and endothelial function. Am J Hypertens. 2011;24:770–4.

    Article  CAS  Google Scholar 

  26. Tanaka A, Tomiyama H, Maruhashi T, Matsuzawa Y, Miyoshi T, Kabutoya T, et al. Physiological diagnostic criteria for vascular failure. Hypertension. 2018;72:1060–71.

    Article  CAS  Google Scholar 

  27. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97.

  28. American Diabetes Association: Clinical practice recommendations 1999. Diabetes Care. 1999;22 Suppl 1:S1–S114.

  29. Gokce N, Holbrook M, Duffy SJ, Demissie S, Cupples LA, Biegelsen E, et al. Effects of race and hypertension on flow-mediated and nitroglycerin-mediated dilation of the brachial artery. Hypertension. 2001;38:1349–54.

    Article  CAS  Google Scholar 

  30. Higashi Y, Kihara Y, Noma K. Endothelial dysfunction and hypertension in aging. Hypertens Res. 2012;35:1039–47.

    Article  CAS  Google Scholar 

  31. Hishikawa K, Oemar BS, Yang Z, Luscher TF. Pulsatile stretch stimulates superoxide production and activates nuclear factor-kappa B in human coronary smooth muscle. Circ Res. 1997;81:797–803.

    Article  CAS  Google Scholar 

  32. Castier Y, Brandes RP, Leseche G, Tedgui A, Lehoux S. p47phox-dependent NADPH oxidase regulates flow-induced vascular remodeling. Circ Res. 2005;97:533–40.

    Article  CAS  Google Scholar 

  33. Yano Y, Stamler J, Garside DB, Daviglus ML, Franklin SS, Carnethon MR, et al. Isolated systolic hypertension in young and middle-aged adults and 31-year risk for cardiovascular mortality: the Chicago Heart Association Detection Project in Industry study. J Am Coll Cardiol. 2015;65:327–35.

    Article  Google Scholar 

  34. Flint AC, Conell C, Ren X, Banki NM, Chan SL, Rao VA, et al. Effect of systolic and diastolic blood pressure on cardiovascular outcomes. N Engl J Med. 2019;381:243–51.

    Article  Google Scholar 

  35. Choi YJ, Kim SH, Kang SH, Yoon CH, Lee HY, Youn TJ, et al. Reconsidering the cut-off diastolic blood pressure for predicting cardiovascular events: a nationwide population-based study from Korea. Eur Heart J. 2019;40:724–31.

    Article  Google Scholar 

  36. Kaneko H, Itoh H, Yotsumoto H, Kiriyama H, Kamon T, Fujiu K, et al. Association of isolated diastolic hypertension based on the cutoff value in the 2017 American College of Cardiology/American Heart Association blood pressure guidelines with subsequent cardiovascular events in the general population. J Am Heart Assoc. 2020;9:e017963.

    Article  Google Scholar 

  37. Pescatello LS, MacDonald HV, Ash GI, Lamberti LM, Farquhar WB, Arena R, et al. Assessing the existing professional exercise recommendations for hypertension: a review and recommendations for future research priorities. Mayo Clin Proc. 2015;90:801–12.

    Article  Google Scholar 

  38. Neter JE, Stam BE, Kok FJ, Grobbee DE, Geleijnse JM. Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2003;42:878–84.

    Article  CAS  Google Scholar 

  39. Halperin RO, Gaziano JM, Sesso HD. Smoking and the risk of incident hypertension in middle-aged and older men. Am J Hypertens. 2008;21:148–52.

    Article  Google Scholar 

  40. Higashi Y, Sasaki S, Kurisu S, Yoshimizu A, Sasaki N, Matsuura H, et al. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. Circulation. 1999;100:1194–202.

    Article  CAS  Google Scholar 

  41. Sasaki S, Higashi Y, Nakagawa K, Kimura M, Noma K, Sasaki S, et al. A low-calorie diet improves endothelium-dependent vasodilation in obese patients with essential hypertension. Am J Hypertens. 2002;15:302–9. 4 Pt 1.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Miki Kumiji, Megumi Wakisaka, Ki-ichiro Kawano and Satoko Michiyama for their excellent secretarial assistance. FMD-J investigators: Takayuki Hidaka, MD, PhD; Shuji Nakamura, MD, PhD; Junko Soga, MD, PhD; Yuichi Fujii, MD, PhD; Naomi Idei, MD; Noritaka Fujimura, MD, PhD; Shinsuke Mikami, MD, PhD; Yumiko Iwamoto, MD; Akimichi Iwamoto, MD, PhD; Takeshi Matsumoto, MD, PhD; and Nozomu Oda, MD, PhD (Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan); Kana Kanai, PhD, and Haruka Morimoto, PhD (Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan); Tomohisa Sakashita, MD, PhD, and Yoshiki Kudo, MD, PhD (Department of Obstetrics and Gynecology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan); Taijiro Sueda, MD, PhD (Department of Surgery, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan); Hirofumi Tomiyama, MD, PhD, and Akira Yamashina, MD, PhD (Department of Cardiology, Tokyo Medical University, Tokyo, Japan); Bonpei Takase, MD, PhD (Division of Biomedical Engineering, National Defense Medical College Research Institute, Tokorozawa, Japan); Takahide Kohro, MD, PhD (Department of Cardiology, Tokyo Medical University, Tokyo, Japan); Toru Suzuki, MD, PhD (Cardiovascular Medicine, University of Leicester, Leicester, UK); Tomoko Ishizu, MD, PhD (Cardiovascular Division, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan); Shinichiro Ueda, MD, PhD (Department of Clinical Pharmacology and Therapeutics, University of the Ryukyu School of Medicine, Okinawa, Japan); Tsutomu Yamazaki, MD, PhD (Clinical Research Support Center, Faculty of Medicine, The University of Tokyo, Tokyo, Japan); Tomoo Furumoto, MD, PhD (Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Hokkaido, Japan); Kazuomi Kario, MD, PhD (Division of Cardiovascular Medicine, Jichi Medical University School of Medicine, Tochigi, Japan); Teruo Inoue, MD, PhD (Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Tochigi, Japan); Shinji Koba, MD, PhD (Department of Medicine, Division of Cardiology, Showa University School of Medicine, Tokyo, Japan); Kentaro Watanabe, MD, PhD (Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology (DNHMED), Yamagata University School of Medicine, Yamagata, Japan); Yasuhiko Takemoto, MD, PhD (Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medicine, Osaka, Japan); Takuzo Hano, MD, PhD (Department of Medical Education and Population-based Medicine, Postgraduate School of Medicine, Wakayama Medical University, Wakayama, Japan); Masataka Sata, MD, PhD (Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan); Yutaka Ishibashi, MD, PhD (Department of General Medicine, Shimane University Faculty of Medicine, Izumo, Japan); Koichi Node, MD, PhD (Department of Cardiovascular and Renal Medicine, Saga University, Saga, Japan); Koji Maemura, MD, PhD (Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan); Yusuke Ohya, MD, PhD (The Third Department of Internal Medicine, University of the Ryukyus, Okinawa, Japan); Taiji Furukawa, MD, PhD (Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan); Hiroshi Ito, MD, PhD (Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan); and Hisao Ikeda, MD, PhD (Faculty of Fukuoka Medical Technology, Teikyo University, Omuta, Japan).

Funding

Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (18590815 and 21590898 to YH; 16K19408 and 19K17565 to TM) and a Grant-in-Aid of the Japanese Arteriosclerosis Prevention Fund (to YH).

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Authors and Affiliations

  1. Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Yiming Han, Tatsuya Maruhashi, Shinji Kishimoto, Farina Mohamad Yusoff & Yukihito Higashi

  2. Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan

    Masato Kajikawa & Yukihito Higashi

  3. Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Takayuki Yamaji, Takahiro Harada, Yu Hashimoto & Yukiko Nakano

  4. Department of Gastroenterology and Metabolism, Biomedical Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Kazuaki Chayama

  5. Department of Stem Cell Biology and Medicine, Graduate School of Biomedical and Sciences, Hiroshima University, Hiroshima, Japan

    Ayumu Nakashima

  6. Department of Rehabilitation, Faculty of General Rehabilitation, Hiroshima International University, Hiroshima, Japan

    Chikara Goto

  7. Department of Biostatistics, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan

    Kenichi Yoshimura

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  1. Yiming Han
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Han, Y., Maruhashi, T., Kajikawa, M. et al. Isolated diastolic hypertension is not associated with endothelial dysfunction. Hypertens Res 45, 698–707 (2022). https://doi.org/10.1038/s41440-022-00854-y

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