Old and New Molecular Targets in the Treatment of Hypertension
By:
Laisel Martinez DeWitt Daughtry Family Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida

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  • 1.

    Magnussen C, Ojeda FM, Leong DP, Alegre-Diaz J, Amouyel P, Aviles-Santa L, et al.; Global Cardiovascular Risk Consortium: Global effect of modifiable risk factors on cardiovascular disease and mortality. N Engl J Med 389: 12731285, 2023 10.1056/NEJMoa2206916 PubMed

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  • 2.

    Garofalo C, Borrelli S, Pacilio M, Minutolo R, Chiodini P, De Nicola L, et al.: Hypertension and prehypertension and prediction of development of decreased estimated GFR in the general population: A meta-analysis of cohort studies. Am J Kidney Dis 67: 8997, 2016 10.1053/j.ajkd.2015.08.027 PubMed

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  • 3.

    Doumas M, Tsioufis C, Fletcher R, Amdur R, Faselis C, Papademetriou V: Time in therapeutic range, as a determinant of all-cause mortality in patients with hypertension. J Am Heart Assoc 6: e007131, 2017 10.1161/JAHA.117.007131 PubMed

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  • 4.

    Hardy ST, Jaeger BC, Foti K, Ghazi L, Wozniak G, Muntner P: Trends in blood pressure control in US adults with hypertension, 2013–2014 to 2021–2023. Am J Hypertens 38: hpae141, 2024 10.1093/ajh/hpae141 PubMed

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  • 5.

    Fryar CD, Kit B, Carroll MD, Afful J: Hypertension prevalence, awareness, treatment, and control among adults age 18 and older: United States, August 2021–August 2023. NCHS Data Brief 511, Hyattsville, MD, National Center for Health Statistics, 2024 10.15620/cdc/164016

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    Ebinger JE, Gluckman TJ, Magraner J, Chiu ST, Rider D, Thomas C, et al.: Characterization of individuals with apparent resistant hypertension using contemporary guidelines: Insights from CV-QUIC. Hypertension 80: 18451855, 2023 10.1161/HYPERTENSIONAHA.123.20894 PubMed

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  • 7.

    Holmes HR, Li Q, Xu K, Kim S, Richards EM, Keeley EC, et al.: Antihypertensive medication adherence trends by sex and drug class: A pilot study. Am Heart J Plus 5: 100023, 2021 10.1016/j.ahjo.2021.100023 PubMed

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  • 8.

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  • 9.

    Bergland OU, Halvorsen LV, Søraas CL, Hjørnholm U, Kjær VN, Rognstad S, et al.: Detection of nonadherence to antihypertensive treatment by measurements of serum drug concentrations. Hypertension 78: 617628, 2021 10.1161/HYPERTENSIONAHA.121.17514 PubMed

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    Joseph JJ, Pohlman NK, Zhao S, Kline D, Brock G, Echouffo-Tcheugui JB, et al.: Association of serum aldosterone and plasma renin activity with ambulatory blood pressure in African Americans: The Jackson Heart Study. Circulation 143: 23552366, 2021 10.1161/CIRCULATIONAHA.120.050896 PubMed

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  • 11.

    Jędrusik P, Symonides B, Lewandowski J, Gaciong Z: The effect of antihypertensive medications on testing for primary aldosteronism. Front Pharmacol 12: 684111, 2021 10.3389/fphar.2021.684111 PubMed

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    Kuralay A, McDonough MC, Resch JM: Control of sodium appetite by hindbrain aldosterone-sensitive neurons. Mol Cell Endocrinol 592: 112323, 2024 10.1016/j.mce.2024.112323 PubMed

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    Teixeira LB, Parreiras-E-Silva LT, Bruder-Nascimento T, Duarte DA, Simões SC, Costa RM, et al.: Ang-(1-7) is an endogenous beta-arrestin-biased agonist of the AT(1) receptor with protective action in cardiac hypertrophy. Sci Rep 7: 11903, 2017 10.1038/s41598-017-12074-3 PubMed

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    Ranjit A, Khajehpour S, Aghazadeh-Habashi A: Update on angiotensin II subtype 2 receptor: Focus on peptide and nonpeptide agonists. Mol Pharmacol 99: 469487, 2021 10.1124/molpharm.121.000236 PubMed

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    Messerli FH, Bangalore S, Bavishi C, Rimoldi SF: Angiotensin-converting enzyme inhibitors in hypertension: To use or not to use? J Am Coll Cardiol 71: 14741482, 2018 10.1016/j.jacc.2018.01.058 PubMed

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    Paz MA, de-La-Sierra A, Sáez M, Barceló MA, Rodríguez JJ, Castro S, et al.: Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement. Medicine (Baltimore) 95: e4071, 2016 10.1097/MD.0000000000004071 PubMed

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  • 19.

    Takahashi S, Katada J, Daida H, Kitamura F, Yokoyama K: Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: A systematic review and meta-analysis. J Hum Hypertens 30: 534542, 2016 10.1038/jhh.2015.119 PubMed

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  • 20.

    Dreier R, Andersen UB, Forman JL, Sheykhzade M, Egfjord M, Jeppesen JL: Effect of increased potassium intake on adrenal cortical and cardiovascular responses to angiotensin II: A randomized crossover study. J Am Heart Assoc 10: e018716, 2021 10.1161/JAHA.120.018716 PubMed

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    Hoorn EJ, Gritter M, Cuevas CA, Fenton RA: Regulation of the renal NaCl cotransporter and its role in potassium homeostasis. Physiol Rev 100: 321356, 2020 10.1152/physrev.00044.2018 PubMed

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  • 23.

    Burnier M: Should we eat more potassium to better control blood pressure in hypertension? Nephrol Dial Transplant 34: 184193, 2019 10.1093/ndt/gfx340 PubMed

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    Ernst ME, Fravel MA: Thiazide and the thiazide-like diuretics: Review of hydrochlorothiazide, chlorthalidone, and indapamide. Am J Hypertens 35: 573586, 2022 10.1093/ajh/hpac048 PubMed

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    Huart J, Persu A, Lengele JP, Krzesinski JM, Jouret F, Stergiou GS: Pathophysiology of the nondipping blood pressure pattern. Hypertension 80: 719729, 2023 10.1161/HYPERTENSIONAHA.122.19996 PubMed

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  • 35.

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  • 36.

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    Perry RJ, Shulman GI: Sodium-glucose cotransporter-2 inhibitors: Understanding the mechanisms for therapeutic promise and persisting risks. J Biol Chem 295: 1437914390, 2020 10.1074/jbc.REV120.008387 PubMed

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    Ahwin P, Martinez D: The relationship between SGLT2 and systemic blood pressure regulation. Hypertens Res 47: 20942103, 2024 10.1038/s41440-024-01723-6 PubMed

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    Zhang R, Xie Q, Lu X, Fan R, Tong N: Research advances in the anti-inflammatory effects of SGLT inhibitors in type 2 diabetes mellitus. Diabetol Metab Syndr 16: 99, 2024 10.1186/s13098-024-01325-9 PubMed

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    Bakris GL, Saxena M, Gupta A, Chalhoub F, Lee J, Stiglitz D, et al.; KARDIA-1 Study Group: RNA interference with zilebesiran for mild to moderate hypertension: The KARDIA-1 randomized clinical trial. JAMA 331: 740749, 2024 10.1001/jama.2024.0728 PubMed

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    Bakris GL: Zilebesiran in combination with a standard-of-care antihypertensive in patients with inadequately controlled hypertension - KARDIA-2. Presented at the 2024 Scientific Session of the American College of Cardiology, Atlanta, GA, April 6–8, 2024

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    Saxena M, Aswad A, Badariene J, Karim A, Sia YT, Stiglitz D, et al.: Subgroup results from KARDIA-2: Impact of demographic and baseline disease characteristics on zilebesiran response in patients with hypertension uncontrolled by a standard oral antihypertensive. Eur Heart J 45: ehae666.2593, 2024 https://doi.org/10.1093/eurheartj/ehae666.2593

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