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Cardiovascular risk in patients receiving antihypertensive drug treatment from the perspective of endothelial function

Hypertension Research volume 45, pages 1322–1333 (2022)Cite this article

Abstract

Blood-pressure-lowering therapy with antihypertensive drugs can reduce the risk of cardiovascular morbidity and mortality in patients with hypertension. However, patients treated with antihypertensive drugs generally have a worse prognosis than untreated individuals. Consistent with the results obtained from epidemiological studies, a clinical study showed that endothelial function was impaired more in treated patients with hypertension than in untreated individuals with the same blood pressure level, suggesting that blood-pressure-lowering therapy with currently available antihypertensive drugs cannot restore endothelial function to the level of that in untreated individuals. Several mechanisms of endothelial dysfunction in treated patients are postulated: irreversible damage to the endothelium caused by higher cumulative elevated blood pressure exposure over time; the persistence of the primary causes of hypertension even after the initiation of antihypertensive drug treatment, including an activated renin-angiotensin-aldosterone system, oxidative stress, and inflammation; and higher global cardiovascular risk related not only to conventional cardiovascular risk factors but also to undetectable nonconventional risk factors. Lifestyle modifications/nonpharmacological interventions should be strongly recommended for both untreated and treated individuals with hypertension. Lifestyle modifications/nonpharmacological interventions may directly correct the primary causes of hypertension, which can improve endothelial function and consequently reduce cardiovascular risk regardless of the use or nonuse of antihypertensive drugs.

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References

  1. Ikeda N, Inoue M, Iso H, Ikeda S, Satoh T, Noda M, et al. Adult mortality attributable to preventable risk factors for non-communicable diseases and injuries in Japan: a comparative risk assessment. PLoS Med. 2012;9:e1001160.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Staessen JA, Wang JG, Thijs L. Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet. 2001;358:1305–15.

    Article  CAS  PubMed  Google Scholar 

  3. Bundy JD, Li C, Stuchlik P, Bu X, Kelly TN, Mills KT, et al. Systolic blood pressure reduction and risk of cardiovascular disease and mortality: a systematic review and network meta-analysis. JAMA Cardiol. 2017;2:775–81.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Group SR, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103–16.

    Article  CAS  Google Scholar 

  5. Zhang W, Zhang S, Deng Y, Wu S, Ren J, Sun G, et al. Trial of intensive blood-pressure control in older patients with hypertension. N Engl J Med. 2021;385:1268–79.

    Article  CAS  PubMed  Google Scholar 

  6. Blacher J, Evans A, Arveiler D, Amouyel P, Ferrieres J, Bingham A, et al. Residual cardiovascular risk in treated hypertension and hyperlipidaemia: the PRIME Study. J Hum Hypertens. 2010;24:19–26.

    Article  CAS  PubMed  Google Scholar 

  7. Asayama K, Satoh M, Murakami Y, Ohkubo T, Nagasawa SY, Tsuji I, et al. Cardiovascular risk with and without antihypertensive drug treatment in the Japanese general population: participant-level meta-analysis. Hypertension. 2014;63:1189–97.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, et al. Endothelial function is impaired in patients receiving antihypertensive drug treatment regardless of blood pressure level: FMD-J Study (Flow-Mediated Dilation Japan). Hypertension. 2017;70:790–7.

    Article  CAS  PubMed  Google Scholar 

  11. Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet. 1989;2:997–1000.

    Article  CAS  PubMed  Google Scholar 

  12. Vane JR, Anggard EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med. 1990;323:27–36.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  16. Griendling KK, Camargo LL, Rios FJ, Alves-Lopes R, Montezano AC, Touyz RM. Oxidative stress and hypertension. Circulation Res. 2021;128:993–1020.

    Article  CAS  PubMed  Google Scholar 

  17. Harrison DG, Coffman TM, Wilcox CS. Pathophysiology of hypertension: the mosaic theory and beyond. Circulation Res. 2021;128:847–63.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang Y, Murugesan P, Huang K, Cai H. NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets. Nat Rev Cardiol. 2020;17:170–94.

    Article  CAS  PubMed  Google Scholar 

  19. Vanhoutte PM, Boulanger CM. Endothelium-dependent responses in hypertension. Hypertension Res. 1995;18:87–98.

    Article  CAS  Google Scholar 

  20. Taddei S, Virdis A, Ghiadoni L, Sudano I, Salvetti A. Endothelial dysfunction in hypertension. J Cardiovasc Pharmacol. 2001;38(Suppl 2):S11–14.

    Article  CAS  PubMed  Google Scholar 

  21. Schulz E, Gori T, Munzel T. Oxidative stress and endothelial dysfunction in hypertension. Hypertension Res. 2011;34:665–73.

    Article  CAS  Google Scholar 

  22. Li Q, Youn JY, Cai H. Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension. J Hypertens. 2015;33:1128–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Vanhoutte PM, Shimokawa H, Feletou M, Tang EH. Endothelial dysfunction and vascular disease – a 30th anniversary update. Acta Physiol. 2017;219:22–96.

    Article  CAS  Google Scholar 

  24. Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323:22–27.

    Article  CAS  PubMed  Google Scholar 

  25. Linder L, Kiowski W, Buhler FR, Luscher TF. Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. Circulation. 1990;81:1762–7.

    Article  CAS  PubMed  Google Scholar 

  26. 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  PubMed  Google Scholar 

  27. Treasure CB, Klein JL, Vita JA, Manoukian SV, Renwick GH, Selwyn AP, et al. Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels. Circulation. 1993;87:86–93.

    Article  CAS  PubMed  Google Scholar 

  28. Egashira K, Suzuki S, Hirooka Y, Kai H, Sugimachi M, Imaizumi T, et al. Impaired endothelium-dependent vasodilation of large epicardial and resistance coronary arteries in patients with essential hypertension. Different responses to acetylcholine and substance P. Hypertension. 1995;25:201–6.

    Article  CAS  PubMed  Google Scholar 

  29. Higashi Y, Oshima T, Ozono R, Watanabe M, Matsuura H, Kajiyama G. Effects of L-arginine infusion on renal hemodynamics in patients with mild essential hypertension. Hypertension. 1995;25(4 Pt 2):898–902.

    Article  CAS  PubMed  Google Scholar 

  30. Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, et al. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation. 2001;104:191–6.

    Article  CAS  PubMed  Google Scholar 

  31. Higashi Y, Sasaki S, Nakagawa K, Kimura M, Sasaki S, Noma K, et al. Severity of hypertension affects improved resistance artery endothelial function by angiotensin-converting enzyme inhibition. J Cardiovasc Pharmacol. 2002;39:668–76.

    Article  CAS  PubMed  Google Scholar 

  32. 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  PubMed  Google Scholar 

  33. 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  PubMed  Google Scholar 

  34. 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. Hypertension Res. 2015;38:862–8.

    Article  CAS  Google Scholar 

  35. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560–72.

    Article  CAS  PubMed  Google Scholar 

  36. 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  PubMed  Google Scholar 

  37. Lindholm L, Ejlertsson G, Schersten B. High risk of cerebro-cardiovascular morbidity in well treated male hypertensives. A retrospective study of 40-59-year-old hypertensives in a Swedish primary care district. Acta Med Scandinavica. 1984;216:251–9.

    Article  CAS  Google Scholar 

  38. Clausen J, Jensen G. Blood pressure and mortality: an epidemiological survey with 10 years follow-up. J Hum Hypertens. 1992;6:53–59.

    CAS  PubMed  Google Scholar 

  39. Andersson OK, Almgren T, Persson B, Samuelsson O, Hedner T, Wilhelmsen L. Survival in treated hypertension: follow up study after two decades. BMJ. 1998;317:167–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Almgren T, Persson B, Wilhelmsen L, Rosengren A, Andersson OK. Stroke and coronary heart disease in treated hypertension – a prospective cohort study over three decades. J Intern Med. 2005;257:496–502.

    Article  CAS  PubMed  Google Scholar 

  41. D’Agostino RB Sr, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117:743–53.

    Article  PubMed  Google Scholar 

  42. Psaty BM, Furberg CD, Kuller LH, Cushman M, Savage PJ, Levine D, et al. Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study. Arch Intern Med. 2001;161:1183–92.

    Article  CAS  PubMed  Google Scholar 

  43. Chambless LE, Folsom AR, Sharrett AR, Sorlie P, Couper D, Szklo M, et al. Coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC) study. J Clin Epidemiol. 2003;56:880–90.

    Article  PubMed  Google Scholar 

  44. Asayama K, Ohkubo T, Yoshida S, Suzuki K, Metoki H, Harada A, et al. Stroke risk and antihypertensive drug treatment in the general population: the Japan arteriosclerosis longitudinal study. J Hypertens. 2009;27:357–64.

    Article  CAS  PubMed  Google Scholar 

  45. Yasui D, Asayama K, Ohkubo T, Kikuya M, Kanno A, Hara A, et al. Stroke risk in treated hypertension based on home blood pressure: the Ohasama study. Am J Hypertens. 2010;23:508–14.

    Article  PubMed  Google Scholar 

  46. Asayama K. Observational study and participant-level meta-analysis on antihypertensive drug treatment-related cardiovascular risk. Hypertension Res. 2017;40:856–60.

    Article  CAS  Google Scholar 

  47. 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). Hypertension Res. 2019;42:1235–481.

    Article  Google Scholar 

  48. Liu K, Colangelo LA, Daviglus ML, Goff DC, Pletcher M, Schreiner PJ, et al. Can antihypertensive treatment restore the risk of cardiovascular disease to ideal levels?: The Coronary Artery Risk Development in Young Adults (CARDIA) Study and the Multi-Ethnic Study of Atherosclerosis (MESA). J Am Heart Assoc. 2015;4:e002275.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Lieb W, Enserro DM, Sullivan LM, Vasan RS. Residual cardiovascular risk in individuals on blood pressure-lowering treatment. J Am Heart Assoc. 2015;4:e002155.

  50. Madhur MS, Elijovich F, Alexander MR, Pitzer A, Ishimwe J, Van Beusecum JP, et al. Hypertension: do inflammation and immunity hold the key to solving this epidemic? Circulation Res. 2021;128:908–33.

    Article  CAS  PubMed  Google Scholar 

  51. Virdis A, Ghiadoni L, Taddei S. Effects of antihypertensive treatment on endothelial function. Curr Hypertens Rep. 2011;13:276–81.

    Article  CAS  PubMed  Google Scholar 

  52. Fujimura N, Noma K, Hata T, Soga J, Hidaka T, Idei N, et al. Mineralocorticoid receptor blocker eplerenone improves endothelial function and inhibits Rho-associated kinase activity in patients with hypertension. Clin Pharmacol Ther. 2012;91:289–97.

    Article  CAS  PubMed  Google Scholar 

  53. Hirooka Y, Imaizumi T, Masaki H, Ando S, Harada S, Momohara M, et al. Captopril improves impaired endothelium-dependent vasodilation in hypertensive patients. Hypertension. 1992;20:175–80.

    Article  CAS  PubMed  Google Scholar 

  54. Iwatsubo H, Nagano M, Sakai T, Kumamoto K, Morita R, Higaki J. et al. Converting enzyme inhibitor improves forearm reactive hyperemia in essential hypertension. Hypertension. 1997;29(1 Pt 2):286–90.

    Article  CAS  PubMed  Google Scholar 

  55. Li S, Wu Y, Yu G, Xia Q, Xu Y. Angiotensin II receptor blockers improve peripheral endothelial function: a meta-analysis of randomized controlled trials. PLoS One. 2014;9:e90217.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Maruhashi T, Kajikawa M, Kishimoto S, Matsui S, Hashimoto H, Takaeko Y, et al. Relationships between calcium channel blockers and vascular function tests. Am J Hypertens. 2019;32:640–8.

    Article  CAS  PubMed  Google Scholar 

  57. Klungel OH, Stricker BH, Breteler MM, Seidell JC, Psaty BM, de Boer A. Is drug treatment of hypertension in clinical practice as effective as in randomized controlled trials with regard to the reduction of the incidence of stroke? Epidemiology. 2001;12:339–44.

    Article  CAS  PubMed  Google Scholar 

  58. Ibsen H. Antihypertensive treatment and risk of cardiovascular complications: is the cure worse than the disease? J Hypertens. 2009;27:221–3.

    Article  CAS  PubMed  Google Scholar 

  59. Maruhashi T, Hisatome I, Kihara Y, Higashi Y. Hyperuricemia and endothelial function: from molecular background to clinical perspectives. Atherosclerosis. 2018;278:226–31.

    Article  CAS  PubMed  Google Scholar 

  60. Oda N, Kajikawa M, Maruhashi T, Iwamoto Y, Kishimoto S, Matsui S, et al. Endothelial function is impaired in relation to alcohol intake even in the case of light alcohol consumption in Asian men; Flow-mediated Dilation Japan (FMD-J) Study. Int J Cardiol. 2017;230:523–8.

    Article  PubMed  Google Scholar 

  61. Matsui S, Kajikawa M, Maruhashi T, Iwamoto Y, Iwamoto A, Oda N, et al. Decreased frequency and duration of tooth brushing is a risk factor for endothelial dysfunction. Int J Cardiol. 2017;241:30–34.

    Article  PubMed  Google Scholar 

  62. Yamaji T, Harada T, Hashimoto Y, Nakano Y, Kajikawa M, Yoshimura K, et al. Stair climbing activity and vascular function in patients with hypertension. Hypertension Res. 2021;44:1274–82.

    Article  CAS  Google Scholar 

  63. Stergiou GS, Asayama K, Thijs L, Kollias A, Niiranen TJ, Hozawa A, et al. Prognosis of white-coat and masked hypertension: International Database of HOme blood pressure in relation to Cardiovascular Outcome. Hypertension. 2014;63:675–82.

    Article  CAS  PubMed  Google Scholar 

  64. Kabutoya T, Hoshide S, Ogata Y, Eguchi K, Kario K. Masked hypertension defined by home blood pressure monitoring is associated with impaired flow-mediated vasodilatation in patients with cardiovascular risk factors. J Clin Hypertens. 2013;15:630–6.

    Article  Google Scholar 

  65. Imano H, Kitamura A, Sato S, Kiyama M, Ohira T, Yamagishi K, et al. Trends for blood pressure and its contribution to stroke incidence in the middle-aged Japanese population: the Circulatory Risk in Communities Study (CIRCS). Stroke. 2009;40:1571–7.

    Article  PubMed  Google Scholar 

  66. Rumana N, Kita Y, Turin TC, Murakami Y, Sugihara H, Morita Y, et al. Trend of increase in the incidence of acute myocardial infarction in a Japanese population: Takashima AMI Registry, 1990-2001. Am J Epidemiol. 2008;167:1358–64.

    Article  PubMed  Google Scholar 

  67. Turin TC, Kokubo Y, Murakami Y, Higashiyama A, Rumana N, Watanabe M, et al. Lifetime risk of stroke in Japan. Stroke. 2010;41:1552–4.

    Article  PubMed  Google Scholar 

  68. Turin TC, Kokubo Y, Murakami Y, Higashiyama A, Rumana N, Watanabe M, et al. Lifetime risk of acute myocardial infarction in Japan. Circ Cardiovasc Qual Outcomes. 2010;3:701–3.

    Article  PubMed  Google Scholar 

  69. Fujiyoshi A, Ohkubo T, Miura K, Murakami Y, Nagasawa SY, Okamura T, et al. Blood pressure categories and long-term risk of cardiovascular disease according to age group in Japanese men and women. Hypertension Res. 2012;35:947–53.

    Article  Google Scholar 

  70. Takashima N, Ohkubo T, Miura K, Okamura T, Murakami Y, Fujiyoshi A, et al. Long-term risk of BP values above normal for cardiovascular mortality: a 24-year observation of Japanese aged 30 to 92 years. J Hypertens. 2012;30:2299–306.

    Article  CAS  PubMed  Google Scholar 

  71. Craighead DH, Freeberg KA, Seals DR. Vascular endothelial function in midlife/older adults classified according to 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines. J Am Heart Assoc. 2020;9:e016625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Hall ME, Cohen JB, Ard JD, Egan BM, Hall JE, Lavie CJ, et al. Weight-loss strategies for prevention and treatment of hypertension: a scientific statement from the American Heart Association. Hypertension. 2021;78:e38–e50.

    Article  CAS  PubMed  Google Scholar 

  73. Barone Gibbs B, Hivert MF, Jerome GJ, Kraus WE, Rosenkranz SK, Schorr EN, et al. Physical activity as a critical component of first-line treatment for elevated blood pressure or cholesterol: who, what, and how?: A scientific statement from the American Heart Association. Hypertension. 2021;78:e26–e37.

    Article  CAS  PubMed  Google Scholar 

  74. Fiuza-Luces C, Garatachea N, Berger NA, Lucia A. Exercise is the real polypill. Physiology. 2013;28:330–58.

    Article  CAS  PubMed  Google Scholar 

  75. Gielen S, Sandri M, Erbs S, Adams V. Exercise-induced modulation of endothelial nitric oxide production. Curr Pharm Biotechnol. 2011;12:1375–84.

    Article  CAS  PubMed  Google Scholar 

  76. Moriguchi J, Itoh H, Harada S, Takeda K, Hatta T, Nakata T, et al. Low frequency regular exercise improves flow-mediated dilatation of subjects with mild hypertension. Hypertension Res. 2005;28:315–21.

    Article  Google Scholar 

  77. Goto C, Higashi Y, Kimura M, Noma K, Hara K, Nakagawa K, et al. Effect of different intensities of exercise on endothelium-dependent vasodilation in humans: role of endothelium-dependent nitric oxide and oxidative stress. Circulation. 2003;108:530–5.

    Article  PubMed  Google Scholar 

  78. Goto C, Nishioka K, Umemura T, Jitsuiki D, Sakagutchi A, Kawamura M, et al. Acute moderate-intensity exercise induces vasodilation through an increase in nitric oxide bioavailiability in humans. Am J Hypertens. 2007;20:825–30.

    Article  CAS  PubMed  Google Scholar 

  79. Higashi Y. Exercise is a double-edged sword for endothelial function. Hypertension Res. 2016;39:61–63.

    Article  CAS  Google Scholar 

  80. 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  PubMed  Google Scholar 

  81. Vasan RS, Larson MG, Leip EP, Kannel WB, Levy D. Assessment of frequency of progression to hypertension in non-hypertensive participants in the Framingham Heart Study: a cohort study. Lancet. 2001;358:1682–6.

    Article  CAS  PubMed  Google Scholar 

  82. Dyer AR, Liu K, Walsh M, Kiefe C, Jacobs DR Jr, Bild DE. Ten-year incidence of elevated blood pressure and its predictors: the CARDIA study. Coronary Artery Risk Development in (Young) Adults. J Hum Hypertens. 1999;13:13–21.

    Article  CAS  PubMed  Google Scholar 

  83. Sakima A, Satonaka H, Nishida N, Yatsu K, Arima H. Optimal blood pressure targets for patients with hypertension: a systematic review and meta-analysis. Hypertension Res. 2019;42:483–95.

    Article  Google Scholar 

  84. Modena MG, Bonetti L, Coppi F, Bursi F, Rossi R. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol. 2002;40:505–10.

    Article  PubMed  Google Scholar 

  85. Higashi Y, Sasaki S, Nakagawa K, Ueda T, Yoshimizu A, Kurisu S, et al. A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study. J Am Coll Cardiol. 2000;35:284–91.

    Article  CAS  PubMed  Google Scholar 

  86. Ghiadoni L, Magagna A, Versari D, Kardasz I, Huang Y, Taddei S, et al. Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension. 2003;41:1281–6.

    Article  CAS  PubMed  Google Scholar 

  87. Frielingsdorf J, Seiler C, Kaufmann P, Vassalli G, Suter T, Hess OM. Normalization of abnormal coronary vasomotion by calcium antagonists in patients with hypertension. Circulation. 1996;93:1380–7.

    Article  CAS  PubMed  Google Scholar 

  88. Luscher TF, Pieper M, Tendera M, Vrolix M, Rutsch W, van den Branden F, et al. A randomized placebo-controlled study on the effect of nifedipine on coronary endothelial function and plaque formation in patients with coronary artery disease: the ENCORE II study. Eur Heart J. 2009;30:1590–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Mak IT, Boehme P, Weglicki WB. Antioxidant effects of calcium channel blockers against free radical injury in endothelial cells. Correlation of protection with preservation of glutathione levels. Circulation Res. 1992;70:1099–103.

    Article  CAS  PubMed  Google Scholar 

  90. Taddei S, Virdis A, Ghiadoni L, Versari D, Salvetti G, Magagna A, et al. Calcium antagonist treatment by lercanidipine prevents hyperpolarization in essential hypertension. Hypertension. 2003;41:950–5.

    Article  CAS  PubMed  Google Scholar 

  91. Schiffrin EL, Deng LY. Structure and function of resistance arteries of hypertensive patients treated with a beta-blocker or a calcium channel antagonist. J Hypertens. 1996;14:1247–55.

    Article  CAS  PubMed  Google Scholar 

  92. Taddei S, Virdis A, Ghiadoni L, Magagna A, Pasini AF, Garbin U, et al. Effect of calcium antagonist or beta blockade treatment on nitric oxide-dependent vasodilation and oxidative stress in essential hypertensive patients. J Hypertens. 2001;19:1379–86.

    Article  CAS  PubMed  Google Scholar 

  93. Bank AJ, Kelly AS, Thelen AM, Kaiser DR, Gonzalez-Campoy JM. Effects of carvedilol versus metoprolol on endothelial function and oxidative stress in patients with type 2 diabetes mellitus. Am J Hypertens. 2007;20:777–83.

    Article  CAS  PubMed  Google Scholar 

  94. Nishioka K, Nakagawa K, Umemura T, Jitsuiki D, Ueda K, Goto C, et al. Carvedilol improves endothelium-dependent vasodilation in patients with dilated cardiomyopathy. Heart. 2007;93:247–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Megumi Wakisaka, Miki Kumiji, Ki-ichiro Kawano, and Satoko Michiyama for their excellent secretarial assistance.

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

    Tatsuya Maruhashi & Yukihito Higashi

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

    Yukihito Higashi

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Maruhashi, T., Higashi, Y. Cardiovascular risk in patients receiving antihypertensive drug treatment from the perspective of endothelial function. Hypertens Res 45, 1322–1333 (2022). https://doi.org/10.1038/s41440-022-00936-x

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