Hypertensionand Comorbidities: Exploring Interconnections and Advances in Management

Authors

  • Sanat Mahendra Dhoke Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.
  • Mishthi Prajapati Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.
  • Syno Mariam Varghese Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.
  • Anmol Pillai Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.
  • Meensher Thapa Magar Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.
  • SP Srinivas Nayak Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

DOI:

https://doi.org/10.22270/ajprd.v13i1.1513

Abstract

Hypertension (HTN) is a major worldwide health concern, frequently exacerbated by its close links to chronic illnesses like diabetes and asthma. The complex interactions between hypertension and associated comorbidities are examined in this review, with a focus on common pathophysiological processes such as oxidative stress, systemic inflammation, and dysregulated renin-angiotensin-aldosterone system (RAAS) activation. The risk of cardiovascular and renal problems is greatly increased when these linkages are present, especially in those who have diabetes and asthma. In order to lower morbidity and mortality in hypertensive individuals with diabetes, it is vital to achieve strict blood pressure management, as evidenced by large-scale studies like the HOT and ABCD trials. The management of hypertension is further complicated by inflammatory endotypes linked to asthma, which calls for specialised treatment strategies.Significant progress has been made in personalised medicine with recent developments in the treatment of hypertension, such as the use of mineralocorticoid receptor antagonists, endothelin receptor blockers, and novel chronotherapy. These tactics seek to minimise side effects while optimising blood pressure regulation. However, safety issues and the need for more study to confirm these medicines' long-term effectiveness pose challenges to their application. In order to enhance outcomes and lessen the worldwide burden of disease linked to hypertension, this review emphasises the use of specific medicine in the management of hypertension and its comorbidities and promotes a patient-centric approach.

 

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Author Biographies

Sanat Mahendra Dhoke, Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

Mishthi Prajapati, Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

Syno Mariam Varghese, Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

Anmol Pillai, Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

Meensher Thapa Magar, Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

SP Srinivas Nayak , Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

Parul Institute of Pharmacy and Research, Faculty of Pharmacy, Parul University, Vadodara, Gujarat, India.

References

Oparil S, Acelajado MC, Bakris GL, Berlowitz DR, Cífková R, Dominiczak AF, Grassi G, Jordan J, Poulter NR, Rodgers A, Whelton PK. HTN. Nat Rev Dis Primers. 2018 Mar 22;4:18014. doi: 10.1038/nrdp.2018.14. PMID: 29565029; PMCID: PMC6477925.

Forouzanfar MH et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1659–1724 (2016).

Zolotareva O, Saik OV, Königs C, Bragina EY, Goncharova IA, Freidin MB, Dosenko VE, Ivanisenko VA, Hofestädt R. Comorbidity of asthma and Hypertension may be mediated by shared genetic dysregulation and drug side effects. Sci Rep. 2019 Nov 8;9(1):16302. doi: 10.1038/s41598-019-52762-w. PMID: 31705029; PMCID: PMC6841742.

Global strategy for asthma management and prevention. https://ginasthma.org (2017).

Mancia, G., Grassi, G. & Redon, J. (eds) Manual of Hypertension of the European Society of Hypertension, Second Edition, 10.1201/b17072 (CRC Press, 2014).

Dogra S, Ardern CI, Baker J. The relationship between age of asthma onset and cardiovascular disease in Canadians. The Journal of asthma : official journal of the Association for the Care of Asthma. 2007;44:849–854.

Bjermer L. Time for a paradigm shift in asthma treatment: from relieving bronchospasm to controlling systemic inflammation. J Allergy Clin Immunol. 2007;120:1269–1275.

Nelson HS, Weiss ST, Bleecker ER, et al. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15–26.

Lastra G, Syed S, Kurukulasuriya LR, Manrique C, Sowers JR. Type 2 diabetes mellitus and Hypertension: an update. Endocrinol Metab Clin North Am. 2014 Mar;43(1):103-22. doi: 10.1016/j.ecl.2013.09.005. Epub 2013 Dec 12. PMID: 24582094; PMCID: PMC3942662.

Stamler J, Vaccaro O, Neaton JD, et al. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16:434–444.

Hu G, Jousilahti P, Tuomilehto J. Joint effects of history of Hypertension at baseline and Type 2 diabetes at baseline and during follow-up on the risk of coronary heart disease. Eur Heart J. 2007;28:3059–3066.

Sarwar N, Gao P, Seshasai SR, et al. Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215–2222.

Fox CS. Cardiovascular disease risk factors, type 2 diabetes mellitus, and the Framingham Heart Study. Trends Cardiovasc Med. 2010;20:90–95.

Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Updated 2017.

Banday MZ, Sameer AS, Nissar S. Pathophysiology of diabetes: An overview. Avicenna J Med. 2020 Oct 13;10(4):174-188. doi: 10.4103/ajm.ajm_53_20. PMID: 33437689; PMCID: PMC7791288.

Sowers JR. Diabetes mellitus and vascular disease. Hypertension. 2013;61(5):943–7.

Massiera F, Bloch-Faure M, Ceiler D, et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J. 2001;15:2727–2729.

Boustany CM, Bharadwaj K, Daugherty A, et al. Activation of the systemic and adipose reninangiotensin system in rats with diet-induced obesity and Hypertension. Am J PhysiolRegulIntegr Comp Physiol. 2004;287:R943–R949.

Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. 2007;292:C82–97.

Muniyappa R, Quon MJ. Insulin action and insulin resistance in vascular endothelium. Curr Opin Clin NutrMetab Care. 2007;10:523–530.

Song J, Hu X, Riazi S, et al. Regulation of blood pressure, the epithelial sodium channel (ENaC), andother key renal sodium transporters by chronic insulin infusion in rats. Am J Physiol Renal Physiol. 2006;290:F1055–F1064.

Tiwari S, Sharma N, Gill PS, et al. Impaired sodium excretion and increased blood pressure in mice with targeted deletion of renal epithelial insulin receptor. Proc Natl Acad Sci USA. 2008;105:6469–6774.

Muscelli E, Natali A, Bianchi S, et al. Effect of insulin on renal sodium and uric acid handling in essential Hypertension. Am J Hypertens. 1996;9:746–752.

Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood pressure lowering and low-dose aspirin in patients with Hypertension: principal results of the HypertensionOptimalTreatment (HOT) randomised trial. HOT Study Group. Lancet. 1998;351:1755–62.

Tuomilehto J, Rastenyte D, Birkenhäger WH, et al. Effects of calcium-channel blockade in older patients with diabetes and systolic Hypertension. Systolic Hypertension in Europe Trial Investigators. N Engl J Med. 1999;340:677–684.

Curb JD, Pressel SL, Cutler JA, Savage PJ, Applegate WB, Black H, et al. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic Hypertension. JAMA. 1996;276:1886–92.

Schrier RW, Estacio RO, Jeffers B. Appropriate blood pressure control in NIDDM (ABCD) trial. Diabetologia. 1996;39:1646–1654.

Petrie JR, Guzik TJ, Touyz RM. Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. Can J Cardiol. 2018 May;34(5):575-584. doi: 10.1016/j.cjca.2017.12.005. Epub 2017 Dec 11. PMID: 29459239; PMCID: PMC5953551.

N Engl J Med 2019;381:1046-57. DOI: 10.1056/NEJMra1800345

Verdecchia P, Cavallini C, Angeli F. Advances in the Treatment Strategies in Hypertension: Present and Future. J Cardiovasc Dev Dis. 2022 Mar 3;9(3):72. doi: 10.3390/jcdd9030072. PMID: 35323620; PMCID: PMC8949859.

NCD Risk Factor Collaboration (NCD-RisC) Worldwide trends in Hypertension prevalence and progress in treatment and control from 1990 to 2019: A pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;398:957–980. doi: 10.1016/S0140-6736(21)01330-1.

Forouzanfar M.H., Liu P., Roth G.A., Ng M., Biryukov S., Marczak L., Alexander L., Estep K., Abate K.H., Akinyemiju T.F., et al. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990–2015. JAMA. 2017;317:165–182. doi: 10.1001/jama.2016.19043.

Dzau V.J., Balatbat C.A. Future of Hypertension. HTN. 2019;74:450–457. doi: 10.1161/HTNAHA.119.13437.

Tsioufis C., Andrikou I., Thomopoulos C., Syrseloudis D., Stergiou G., Stefanadis C. Increased nighttime blood pressure or nondipping profile for prediction of cardiovascular outcomes. J. Hum. Hypertens. 2011;25:281–293. doi: 10.1038/jhh.2010.113.

Hermida R.C., Ayala D.E., Calvo C., Lopez J.E., Mojon A., Fontao M.J., Soler R., Fernandez J.R. Effects of time of day of treatment on ambulatory blood pressure pattern of patients with resistantHypertension. HTN. 2005;46:1053–1059. doi: 10.1161/01.HYP.0000172757.96281.bf.

Hermida R.C., Ayala D.E., Fontao M.J., Mojon A., Alonso I., Fernandez J.R. Administration-time-dependent effects of spirapril on ambulatory blood pressure in uncomplicated essential HTN. Chronobiol. Int. 2010;27:560–574. doi: 10.3109/07420528.2010.485411.

Morgan T., Anderson A., Jones E. The effect on 24 h blood pressure control of an angiotensin converting enzyme inhibitor (perindopril) administered in the morning or at night. J. Hypertens. 1997;15:205–211. doi: 10.1097/00004872-199715020-00012.

Rahman M., Greene T., Phillips R.A., Agodoa L.Y., Bakris G.L., Charleston J., Contreras G., Gabbai F., Hiremath L., Jamerson K., et al. A trial of 2 strategies to reduce nocturnal blood pressure in blacks with chronic kidney disease. Hypertension. 2013;61:82–88. doi: 10.1161/HTNAHA.112.200477.

Rorie D.A., Rogers A., Mackenzie I.S., Ford I., Webb D.J., Willams B., Brown M., Poulter N., Findlay E., Saywood W., et al. Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: The Treatment In Morning versus Evening (TIME) study. BMJ Open. 2016;6:e010313. doi: 10.1136/bmjopen-2015-010313.

Kaplan N.M. Chlorthalidone versus hydrochlorothiazide: A tale of tortoises and a hare. Hypertension. 2011;58:994–995. doi: 10.1161/HTNAHA.111.183525.

Kurtz T.W. Chlorthalidone: Don’t call it “thiazide-like” anymore. Hypertension. 2010;56:335–337. doi: 10.1161/Hypertension AHA.110.156166.

Agarwal R., ASinha D., Cramer A.E., Balmes-Fenwick M., Dickinson J.H., Ouyang F., Tu W. Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease. N. Engl. J. Med. 2021;385:2507–2519. doi: 10.1056/NEJMoa2110730.

Williams B., MacDonald T.M., Morant S., Webb D.J., Sever P., McInnes G., Ford I., Cruickshank J.K., Caulfield M.J., Salsbury J., et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant Hypertension (PATHWAY-2): A randomised, double-blind, crossover trial. Lancet. 2015;386:2059–2068. doi: 10.1016/S0140-6736(15)00257-3.

Williams B., MacDonald T.M., Morant S.V., Webb D.J., Sever P., McInnes G.T., Ford I., Cruickshank J.K., Caulfield M.J., Padmanabhan S., et al. Endocrine and haemodynamic changes in resistant Hypertension, and blood pressure responses to spironolactone or amiloride: The PATHWAY-2 mechanisms substudies. Lancet Diabetes Endocrinol. 2018;6:464–475. doi: 10.1016/S2213-8587(18)30071-8.

Struthers A., Krum H., Williams G.H. A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin. Cardiol. 2008;31:153–158. doi: 10.1002/clc.20324.

Tam T.S., Wu M.H., Masson S.C., Tsang M.P., Stabler S.N., Kinkade A., Tung A., Tejani A.M. Eplerenone for Hypertension. Cochrane Database Syst. Rev. 2017;2:CD008996. doi: 10.1002/14651858.CD008996.pub2.

Schiffrin E.L. Vascular endothelin in Hypertension. Vascul. Pharmacol. 2005;43:19–29. doi: 10.1016/j.vph.2005.03.004.

Schiffrin E.L. Vascular endothelin in Hypertension. Vascul. Pharmacol. 2005;43:19–29. doi: 10.1016/j.vph.2005.03.004.

Bondurand N., Dufour S., Pingault V. News from the endothelin-3/EDNRB signaling pathway: Role during enteric nervous system development and involvement in neural crest-associated disorders. Dev. Biol. 2018;444((Suppl. 1)):S156–S169. doi: 10.1016/j.ydbio.2018.08.014.

Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:411–415. doi: 10.1038/332411a0.

Mills J., Vardeny O. The Role of Neprilysin Inhibitors in Cardiovascular Disease. Curr. Heart Fail. Rep. 2015;12:389–394. doi: 10.1007/s11897-015-0270-8.

Zanchi A., Maillard M., Burnier M. Recent clinical trials with omapatrilat: New developments. Curr. Hypertens. Rep. 2003;5:346–352. doi: 10.1007/s11906-003-0045-6.

Yandrapalli, S., Pal, S., Nabors, C., & Aronow, W. S. (2018). Drug treatment of Hypertension in older patients with diabetes mellitus. Expert Opinion on Pharmacotherapy, 19(7), 633–642. doi:10.1080/14656566.2018.1456529

Wandile PM. HTN and comorbidities: A silent threat to global health. HypertensComorb. 2024;1(1):1-7.https://doi.org/10.46439/HTN

Published

2025-02-15

How to Cite

Dhoke, S. M., Prajapati, M., Varghese, S. M., Pillai, A., Magar, M. T., & Nayak , S. S. (2025). Hypertensionand Comorbidities: Exploring Interconnections and Advances in Management. Asian Journal of Pharmaceutical Research and Development, 13(1), 110–116. https://doi.org/10.22270/ajprd.v13i1.1513