Association of antihypertensive therapy intensification on blood pressure control and atherosclerotic cardiovascular disease (ASCVD) risk: a retrospective cohort study in Bali, Indonesia
Abstract
Background: Hypertension is a major ASCVD risk factor, especially among elderly and diabetic patients. Appropriately intensifying antihypertensive therapy may improve blood pressure (BP) control and reduce ASCVD risk.
Objective: This study evaluated the effect of antihypertensive therapy intensification on BP outcomes and 10-year ASCVD risk among hypertensive patients in Bali, Indonesia.
Methods: A retrospective cohort study included hypertensive patients aged 40–74 years receiving outpatient care at regional public hospitals in Bali (January–December 2024). Therapy intensification was assessed using a guideline-based treatment intensification (TI) score; primary outcomes were final BP and estimated 10-year ASCVD risk.
Results: Of 191 patients (median age 62 years; 75.9% with type 2 diabetes mellitus), those with appropriate therapy intensification achieved significantly lower systolic BP than those with inappropriate intensification (122.77 vs. 143.28 mmHg; p < 0.001) and were more likely to attain controlled BP (OR = 63.462; 95%CI: 8.017–502.354; p < 0.001; estimate based on a small reference cell). Each 0.1-unit increase in the TI score was associated with a 0.35% reduction in estimated ASCVD risk (p < 0.001).
Conclusion: Appropriate antihypertensive therapy intensification was associated with significantly better blood pressure control, with a non-significant tendency toward below-target BP among patients receiving appropriate intensification.
References
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23. Kim BJ, Cho Y, Hong K, Lee J, Kim J, Choi KH, et al. Treatment Intensification for Elevated Blood Pressure and Risk of Recurrent Stroke. J Am Heart Assoc. 2021;10. https://doi.org/10.1161/JAHA.120.019457
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28. Lee H, Yano Y, Cho SMJ, Heo JE, Kim D-W, Park S, et al. Adherence to Antihypertensive Medication and Incident Cardiovascular Events in Young Adults With Hypertension. Hypertension. 2021;77: 1341-1349. https://doi.org/10.1161/HYPERTENSIONAHA.120.16784
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31. Sun Z. Aging, Arterial Stiffness, and Hypertension. Hypertension. 2015;65: 252-256. https://doi.org/10.1161/HYPERTENSIONAHA.114.03617
32. Harvey A, Montezano AC, Touyz RM. Vascular Biology of Ageing-Implications in Hypertension. J Mol Cell Cardiol. 2015;83: 112-121. https://doi.org/10.1016/j.yjmcc.2015.04.011
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37. Weir CB, Jan A. BMI Classification Percentile and Cut Off Points. StatPearls. 2025.
38. Pan A, Wang Y, Talaei M, Hu FB. Relation of Smoking With Total Mortality and Cardiovascular Events Among Patients With Diabetes Mellitus. Circulation. 2015;132: 1795-1804. https://doi.org/10.1161/CIRCULATIONAHA.115.017926
39. Durand H, Hayes P, Morrissey EC, Newell J, Casey M, Murphy AW, et al. Medication Adherence Among Patients with Apparent Treatment-Resistant Hypertension. J Hypertens. 2017;35: 2346-2357. https://doi.org/10.1097/HJH.0000000000001502
40. De Backer T, Van Nieuwenhuyse B, De Bacquer D. Antihypertensive Treatment in a General Uncontrolled Hypertensive Population in Belgium and Luxembourg in Primary Care: Therapeutic Inertia and Treatment Simplification. The SIMPLIFY Study. Li Y, editor. PLoS One. 2021;16: e0248471. https://doi.org/10.1371/journal.pone.0248471
41. Montano D. Public Health Impact of Antihypertensive Medication Use on Arterial Blood Pressure: A Pooled Cross-Sectional Analysis of Population Health Surveys. PLoS One. 2023;18. https://doi.org/10.1371/journal.pone.0290344
42. Park S, Shin E-S, Ihm S-H, Lee H-Y. Optimizing Systolic Blood Pressure Targets for Elderly Hypertensive Patients: A Meta-Analysis of Mortality, Cardiovascular Outcomes, and Adverse Events. Clin Hypertens. 2025;31: 1-11. https://doi.org/10.5646/ch.2025.31.e25
43. Kim BS, Lim YH, Shin J, Shin JH. Association of Systolic Blood Pressure Target and Variability with Long-Term Clinical Outcomes in Patients Undergoing Percutaneous Coronary Intervention. Clin Hypertens. 2025;31: 1-13. https://doi.org/10.5646/ch.2025.31.e13
44. 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: 243-251. https://doi.org/10.1056/NEJMoa1803180
45. Levy PD, Willock RJ, Burla M, Brody A, Mahn J, Marinica A, et al. Total Antihypertensive Therapeutic Intensity Score and Its Relationship to Blood Pressure Reduction. J Am Soc Hypertens. 2016;10: 906-916. https://doi.org/10.1016/j.jash.2016.10.005
46. Canoy D, Copland E, Nazarzadeh M, Ramakrishnan R, Pinho-Gomes AC, Salam A, et al. Antihypertensive Drug Effects on Long-Term Blood Pressure: An Individual-Level Data Meta-Analysis of Randomised Clinical Trials. Heart. 2022;108: 1281-1289. https://doi.org/10.1136/heartjnl-2021-320171
47. Hameed MA, Dasgupta I. Medication adherence and treatment-resistant hypertension: a review. Drugs Context. 2019;8: 1-11. doi:10.7573/dic.212560
https://doi.org/10.7573/dic.212560
48. Albasri A, Hattle M, Koshiaris C, Dunnigan A, Paxton B, Fox SE, et al. Association Between Antihypertensive Treatment and Adverse Events: Systematic Review and Meta-Analysis. BMJ. 2021; n189. https://doi.org/10.1136/bmj.n189
49. Klop M, Maier AB, Meskers CGM, Steiner JM, Helsloot DO, van Wezel RJA, et al. The Effect of A Change in Antihypertensive Treatment on Orthostatic Hypotension in Older Adults: A Systematic Review and Meta-Analysis. Exp Gerontol. 2024;193: 112461. https://doi.org/10.1016/j.exger.2024.112461
50. Coca A, Borghi C, Stergiou GS, Khan I, Koumas A, Blacher J, et al. Estimated Impact of Guidelines-Based Initiation of Dual Antihypertensive Therapy on Long-Term Cardiovascular Outcomes In 1.1 Million Individuals. Eur Hear J - Cardiovasc Pharmacother. 2024;10: 697-707. https://doi.org/10.1093/ehjcvp/pvae048
2. Masenga SK, Kirabo A. Hypertensive Heart Disease: Risk Factors, Complications and Mechanisms. Front Cardiovasc Med. 2023;10: 1-16. https://doi.org/10.3389/fcvm.2023.1205475
3. PERKI. Guidelines for the Prevention of Atherosclerotic Cardiovascular Disease. Arso IA, editor. Indonesian Society of Cardiovascular Specialists. Perhimpunan Dokter Spesialis Kardiovaskular Indonesia; 2022.
4. World Health Organization. Global report on hypertension: The race against a silent killer. World Health Organization. 2023.
5. Health Development Policy Agency. Indonesia Health Survey 2023. Jakarta: Ministry of Health of Indonesia; 2023.
6. Nurbaiti, Noor NN, Arsin AA, Andi Zulkifli, Arifin Seweng, Suryani Tawali. Analysing The Role of Lifestyle Factors on Hypertension Among Rural Indonesian Adults: A Case-Control Study. Natl J Community Med. 2024;15: 167-174. https://doi.org/10.55489/njcm.150320243633
7. Rachmawati E, Riskiyah, Novindra QA, Syarifah NA, Aisy NR. Association Between Lifestyle Factors and Hypertension Control in Indonesian Primary Healthcare Settings: A Cross-Sectional Study. Malaysian Fam Physician. 2024;19: 18. https://doi.org/10.51866/oa.409
8. Jebari-Benslaiman S, Galicia-García U, Larrea-Sebal A, Olaetxea JR, Alloza I, Vandenbroeck K, et al. Pathophysiology of Atherosclerosis. Int J Mol Sci. 2022;23: 3346. https://doi.org/10.3390/ijms23063346
9. Frąk W, Wojtasińska A, Lisińska W, Młynarska E, Franczyk B, Rysz J. Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease. Biomedicines. 2022;10: 1938. https://doi.org/10.3390/biomedicines10081938
10. de Boer IH, Bangalore S, Benetos A, Davis AM, Michos ED, Muntner P, et al. Diabetes and Hypertension: A Position Statement by the American Diabetes Association. Diabetes Care. 2017;40: 1273-1284. https://doi.org/10.2337/dci17-0026
11. Soehnlein O, Lutgens E, Döring Y. Distinct inflammatory pathways shape atherosclerosis in different vascular beds. Eur Heart J. 2025;46: 3261-3272. https://doi.org/10.1093/eurheartj/ehaf054
12. Shenasa M, Shenasa H. Hypertension, left ventricular hypertrophy, and sudden cardiac death. Int J Cardiol. 2017;237: 60-63. https://doi.org/10.1016/j.ijcard.2017.03.002
13. Gronewold J, Kropp R, Lehmann N, Stang A, Mahabadi AA, Kälsch H, et al. Cardiovascular Risk and Atherosclerosis Progression in Hypertensive Persons Treated to Blood Pressure Targets. Hypertension. 2019;74: 1436-1447. https://doi.org/10.1161/HYPERTENSIONAHA.119.13827
14. Alborzi A, Attar A, Sayadi M, Nouri F. The Effects of Intensive Blood Pressure Control on Cardiovascular Outcomes Based on 10-Year ASCVD Risk Score: An Analysis of a Clinical Trial. Dini F, editor. Cardiol Res Pract. 2021;2021: 1-9. https://doi.org/10.1155/2021/6635345
15. Gnilo MR, Gonzales E. PS-P16-5: Atherosclerotic Cardiovascular Disease (ASCVD) Risk Stratification of Hypertensive Adults at A Tertiary Hospital. J Hypertens. 2023;41: e507. https://doi.org/10.1097/01.hjh.0000918092.71134.64
16. Osoro I, Kumar R, Sharma A. Ten-Year Risk Assessment for Cardiovascular Diseases Using ASCVD Risk Estimator Plus: Outcomes from Hypertension and Diabetes Patients. Diabetol Metab Syndr. 2023;15: 216. https://doi.org/10.1186/s13098-023-01170-2
17. Alkhalaf A, Aljabr Q, Al Mulla K, Almubarak D, Khan AS, Al Jaziri ZY, et al. A 10-Year Risk Assessment and Primary Prevention Study of Atherosclerotic Cardiovascular Disease Among Adult Patients in Saudi Arabia: A Cross-Sectional Study. Medicina (B Aires). 2025;61: 132. https://doi.org/10.3390/medicina61010132
18. Muntner P, Jaeger BC, Foti K, Ghazi L, Bundy JD, Chen L, et al. Predicted Cardiovascular Risk by the PREVENT Equations in US Adults With Stage 1 Hypertension. Hypertension. 2024;81: 1976-1985. https://doi.org/10.1161/HYPERTENSIONAHA.124.22998
19. Foti K, Wang D, Tang O, Daya NR, Commodore-Mensah Y, Juraschek SP, et al. Modeling the Impact of Biomarker-Guided Versus ASCVD Risk-Guided Drug Treatment in US Adults With Stage 1 Hypertension: The National Health and Nutrition Examination Survey, 1999 to 2004. Hypertension. 2024;81: 1599-1608. https://doi.org/10.1161/HYPERTENSIONAHA.123.22665
20. Wan KS, Moy FM, Mohd Yusoff MF, Mustapha F, Ismail M, Mat Rifin H, et al. Treatment intensification and therapeutic inertia of antihypertensive therapy among patients with type 2 diabetes and hypertension with uncontrolled blood pressure. Sci Rep. 2024;14: 12625. https://doi.org/10.1038/s41598-024-63617-4
21. Mu L, Mukamal KJ. Treatment Intensification for Hypertension in US Ambulatory Medical Care. J Am Heart Assoc. 2016;5. https://doi.org/10.1161/JAHA.116.004188
22. Aubert CE, Sussman JB, Hofer TP, Cushman WC, Ha J-K, Min L. Adding a New Medication Versus Maximizing Dose to Intensify Hypertension Treatment in Older Adults. Ann Intern Med. 2021;174: 1666-1673. https://doi.org/10.7326/M21-1456
23. Kim BJ, Cho Y, Hong K, Lee J, Kim J, Choi KH, et al. Treatment Intensification for Elevated Blood Pressure and Risk of Recurrent Stroke. J Am Heart Assoc. 2021;10. https://doi.org/10.1161/JAHA.120.019457
24. Xu W, Goldberg SI, Shubina M, Turchin A. Optimal systolic blood pressure target, time to intensification, and time to follow-up in treatment of hypertension: population based retrospective cohort study. BMJ. 2015;350: h158-h158. https://doi.org/10.1136/bmj.h158
25. Kreutz R, Brunström M. Lowering of systolic blood pressure with ESPRIT along the BPROAD: the lower the better? Clin Hypertens. 2025;31. https://doi.org/10.5646/ch.2025.31.e20
26. Kim H-J, Kim BS, Kim H, Lee J, Shin J-H, Sung K-C. Impact of blood pressure and medication adherence on clinical outcomes in patients with hypertension. Front Med. 2025;12.
https://doi.org/10.3389/fmed.2025.1564791
27. Arwinda P, Hendra P, Virginia DM. The Effect of Adherence to Antihypertensive Therapy and Cardiovascular Risk Among Hypertensive Patients in Purworejo Regency. J Pharm Sci Community. 2024;21: 190-199. https://doi.org/10.24071/jpsc.007334
28. Lee H, Yano Y, Cho SMJ, Heo JE, Kim D-W, Park S, et al. Adherence to Antihypertensive Medication and Incident Cardiovascular Events in Young Adults With Hypertension. Hypertension. 2021;77: 1341-1349. https://doi.org/10.1161/HYPERTENSIONAHA.120.16784
29. Lukito AA, Harmeiwaty E, Hustrini NM. 2019 Hypertension Management Consensus. Indones Soc Hypertens. Jakarta; 2019.
30. The WHO CVD Risk Chart Working Group. WHO updates Cardiovascular Risk Charts: South-East Asia. In: World Health Organization [Internet]. 2019. Available: https://cdn.who.int/media/docs/default-source/ncds/cardiovascular-diseases/southeast-asia--corrected.pdf?sfvrsn=e7994290_0
31. Sun Z. Aging, Arterial Stiffness, and Hypertension. Hypertension. 2015;65: 252-256. https://doi.org/10.1161/HYPERTENSIONAHA.114.03617
32. Harvey A, Montezano AC, Touyz RM. Vascular Biology of Ageing-Implications in Hypertension. J Mol Cell Cardiol. 2015;83: 112-121. https://doi.org/10.1016/j.yjmcc.2015.04.011
33. Kim JH, Thiruvengadam R. Hypertension in an Ageing Population: Diagnosis, Mechanisms, Collateral Health Risks, Treatments, and Clinical Challenges. Ageing Res Rev. 2024;98: 102344. https://doi.org/10.1016/j.arr.2024.102344
34. Oliveros E, Patel H, Kyung S, Fugar S, Goldberg A, Madan N, et al. Hypertension in Older Adults: Assessment, Management, and Challenges. Clin Cardiol. 2020;43: 99-107. https://doi.org/10.1002/clc.23303
35. Żurański W, Nowak J, Danikiewicz A, Zubelewicz-Szkodzińska B, Hudzik B. Assessing Cardiovascular Risk in Geriatric Patients Without Atherosclerotic Cardiovascular Disease. J Clin Med. 2024;13: 7133. https://doi.org/10.3390/jcm13237133
36. Tu Q, Hyun K, Lin S, Hafiz N, Manandi D, Li E, et al. Impacts of Hypertension and Diabetes on The Incidence of Cardiovascular Diseases and All-Cause Mortality: Findings from The China Health and Retirement Longitudinal Study Cohort. J Hypertens. 2025;43: 623-630. https://doi.org/10.1097/HJH.0000000000003946
37. Weir CB, Jan A. BMI Classification Percentile and Cut Off Points. StatPearls. 2025.
38. Pan A, Wang Y, Talaei M, Hu FB. Relation of Smoking With Total Mortality and Cardiovascular Events Among Patients With Diabetes Mellitus. Circulation. 2015;132: 1795-1804. https://doi.org/10.1161/CIRCULATIONAHA.115.017926
39. Durand H, Hayes P, Morrissey EC, Newell J, Casey M, Murphy AW, et al. Medication Adherence Among Patients with Apparent Treatment-Resistant Hypertension. J Hypertens. 2017;35: 2346-2357. https://doi.org/10.1097/HJH.0000000000001502
40. De Backer T, Van Nieuwenhuyse B, De Bacquer D. Antihypertensive Treatment in a General Uncontrolled Hypertensive Population in Belgium and Luxembourg in Primary Care: Therapeutic Inertia and Treatment Simplification. The SIMPLIFY Study. Li Y, editor. PLoS One. 2021;16: e0248471. https://doi.org/10.1371/journal.pone.0248471
41. Montano D. Public Health Impact of Antihypertensive Medication Use on Arterial Blood Pressure: A Pooled Cross-Sectional Analysis of Population Health Surveys. PLoS One. 2023;18. https://doi.org/10.1371/journal.pone.0290344
42. Park S, Shin E-S, Ihm S-H, Lee H-Y. Optimizing Systolic Blood Pressure Targets for Elderly Hypertensive Patients: A Meta-Analysis of Mortality, Cardiovascular Outcomes, and Adverse Events. Clin Hypertens. 2025;31: 1-11. https://doi.org/10.5646/ch.2025.31.e25
43. Kim BS, Lim YH, Shin J, Shin JH. Association of Systolic Blood Pressure Target and Variability with Long-Term Clinical Outcomes in Patients Undergoing Percutaneous Coronary Intervention. Clin Hypertens. 2025;31: 1-13. https://doi.org/10.5646/ch.2025.31.e13
44. 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: 243-251. https://doi.org/10.1056/NEJMoa1803180
45. Levy PD, Willock RJ, Burla M, Brody A, Mahn J, Marinica A, et al. Total Antihypertensive Therapeutic Intensity Score and Its Relationship to Blood Pressure Reduction. J Am Soc Hypertens. 2016;10: 906-916. https://doi.org/10.1016/j.jash.2016.10.005
46. Canoy D, Copland E, Nazarzadeh M, Ramakrishnan R, Pinho-Gomes AC, Salam A, et al. Antihypertensive Drug Effects on Long-Term Blood Pressure: An Individual-Level Data Meta-Analysis of Randomised Clinical Trials. Heart. 2022;108: 1281-1289. https://doi.org/10.1136/heartjnl-2021-320171
47. Hameed MA, Dasgupta I. Medication adherence and treatment-resistant hypertension: a review. Drugs Context. 2019;8: 1-11. doi:10.7573/dic.212560
https://doi.org/10.7573/dic.212560
48. Albasri A, Hattle M, Koshiaris C, Dunnigan A, Paxton B, Fox SE, et al. Association Between Antihypertensive Treatment and Adverse Events: Systematic Review and Meta-Analysis. BMJ. 2021; n189. https://doi.org/10.1136/bmj.n189
49. Klop M, Maier AB, Meskers CGM, Steiner JM, Helsloot DO, van Wezel RJA, et al. The Effect of A Change in Antihypertensive Treatment on Orthostatic Hypotension in Older Adults: A Systematic Review and Meta-Analysis. Exp Gerontol. 2024;193: 112461. https://doi.org/10.1016/j.exger.2024.112461
50. Coca A, Borghi C, Stergiou GS, Khan I, Koumas A, Blacher J, et al. Estimated Impact of Guidelines-Based Initiation of Dual Antihypertensive Therapy on Long-Term Cardiovascular Outcomes In 1.1 Million Individuals. Eur Hear J - Cardiovasc Pharmacother. 2024;10: 697-707. https://doi.org/10.1093/ehjcvp/pvae048
Published
2026-08-17
How to Cite
PARAHYANGAN, I Putu Denta Nugraha; VIRGINIA, Dita Maria; HENDRA, Phebe.
Association of antihypertensive therapy intensification on blood pressure control and atherosclerotic cardiovascular disease (ASCVD) risk: a retrospective cohort study in Bali, Indonesia.
Acta Pharmaciae Indonesia : Acta Pharm Indo, [S.l.], v. 13, n. 2, p. 17857, aug. 2026.
ISSN 2621-4520.
Available at: <https://jos.unsoed.ac.id/index.php/api/article/view/17857>. Date accessed: 20 aug. 2026.
doi: https://doi.org/10.20884/1.api.2025.13.2.17857.
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