Corresponding author: Kwang-il Kim https://orcid.org/0000-0002-6658-047X Division of Geriatrics, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173beongil, Bundang-gu, Seongnam 13620, Korea E-mail: rk.ca.uns@709mikik
Received 2022 Jun 25; Accepted 2022 Jul 26. Copyright © 2022 Korean Diabetes AssociationThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
The prevalence of diabetes mellitus continues to increase worldwide, and it is a well-established cardiovascular risk factor. Hypertension is also an important cardiovascular risk factor to be controlled and is common among patients with diabetes mellitus. Optimal blood pressure (BP) goals have been the subject of great debate in the management of hypertension among patients with diabetes mellitus. This review provides detailed results from randomized controlled trials and meta-analyses of clinical outcomes according to the target BP in patients with type 2 diabetes mellitus. In addition, the target BP in patients with diabetes mellitus recommended by different guidelines was summarized and presented. A target BP of Keywords: Blood pressure, Cardiovascular diseases, Diabetes mellitus, Hypertension
The prevalence of type 2 diabetes mellitus continues to increase worldwide, with 537 million adults aged 20 to 79 years suffering from diabetes mellitus in 2021. It is estimated that this number will increase to 783 million by 2045 according to the International Diabetes Federation Diabetes Atlas [1]. The prevalence of diabetes mellitus has also consistently increased in the last 7 years in Korea, with an estimated prevalence of 16.7% in 2020 [2]. Diabetes mellitus is a well-established modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD) [3-6] and ranks among the top 10 leading causes of disability-adjusted life-years [7]. High blood pressure (BP) is also the most important risk factor for ASCVD which can be controlled, and hypertension is common among patients with diabetes mellitus [3,8]. According to the Korean hypertension fact sheet 2020, 26% of all hypertensive patients >20 years of age received diabetes mellitus treatment together [9]. In addition, 58.6% of patients with adult diabetes mellitus have hypertension, and only 55.5% of them have hypertension controlled with a BP of 140/85 mm Hg according to the Diabetes Fact Sheet in Korea 2021 [2]. Since uncontrolled high BP is an important risk factor for heart failure (HF), atrial fibrillation, chronic kidney disease, valvular heart disease, dementia, coronary heart disease (CHD), and stroke, it is necessary to properly control BP [3,10]. However, the optimal BP target has been a subject of great debate among patients with diabetes mellitus, and there are differences in the target BP of active control in previous studies and recommendations by each guideline. Considering these differences and the divergence of opinions, clinicians may be confused about BP management in patients with diabetes mellitus.
In this article, we have detailed reviews on how to set the optimal BP target in patients with diabetes mellitus and diabetes mellitus with various comorbidities, based on recent evidence and guidelines.
Optimal target blood pressure (BP) for general and high-risk clinical features in patients with diabetes mellitus. Considering these guidelines and studies, it is important to apply individualized target BP for patients with diabetes mellitus. SBP, systolic blood pressure; DBP, diastolic blood pressure; CV, cardiovascular.
Recommended target BP in patients with diabetes mellitus according to current guidelines
| Guidelines identifier | Year | Target populations | BP thresholds, mm Hg | BP target, mm Hg |
|---|---|---|---|---|
| JNC 8 | 2014 | General | Office ≥140/90 | Office |
| JNC 8 | 2014 | Diabetes | Office ≥140/90 | Office |
| ACC/AHA | 2017 | General | Office ≥130/80 | Office |
| ACC/AHA | 2017 | Diabetes | Office ≥130/80 | Office |
| ESC/ESH | 2018 | General | Office ≥140/90 | Office |
| ESC/ESH | 2018 | Diabetes | Office ≥140/90 | 120/70≤ Office ≤130/80 |
| KSH | 2018 | General | Office >140/90 | Office |
| KSH | 2018 | Diabetes | Office >140/90 | Office |
| KSH | 2018 | Diabetes with CVD b | Office >140/90 | Office |
| NICE | 2019 | General | Office BP ≥140/90 | Office |
| NICE | 2019 | Diabetes | Office BP ≥140/90 | Office |
| ESC/EASD | 2019 | Diabetes | Office ≥140/90 | 120/70≤ Office ≤130/80 |
| KDA | 2021 | Diabetes | - | Office |
| KDA | 2021 | Diabetes with CVD | - | Office |
| ADA | 2022 | Diabetes | Office ≥140/90 | Office |
| ADA | 2022 | Diabetes with higher CV risk c | Office ≥140/90 | Office |
BP, blood pressure; JNC, Joint National Committee; ACC, American College of Cardiology; AHA, American Heart Association; ESC, European Society of Cardiology; ESH, European Society of Hypertension; KSH, Korean Society of Hypertension; CVD, cardiovascular disease; NICE, National Institute for Health and Care Excellence; EASD, European Association for the Study of Diabetes; KDA, Korean Diabetes Association; ADA, American Diabetes Association.
a BP target for all patients; if the treatment is well tolerated, the treated BP target should be office ≤130/80,
b Coronary artery disease, peripheral vascular disease, aortic disease, heart failure, or left ventricular hypertrophy in patients aged ≥50 years,
c Existing atherosclerotic cardiovascular disease (ASCVD) or 10-year ASCVD risk ≥15%.There are representative trials showing CV outcomes and clinical courses according to optimal target BP in patients with diabetes mellitus, and these trials are meaningful enough to be presented as a basis for guidelines. Table 2 summarizes representative clinical trials showing clinical CV outcomes according to the target BP in patients with diabetes mellitus.
Randomized controlled trials about blood pressure control in patients with diabetes mellitus
| Clinical trial | Population | Follow-up | Initial BP, mm Hg | Achieved BP active, mm Hg | Achieved BP control, mm Hg | Clinical outcomes |
|---|---|---|---|---|---|---|
| UKPDS 38, 1998 [5] | 1,148 Hypertensive participants with T2DM aged with 25–65 yr | Median 8.4 yr | Active: 159/94 | 144/82 (target: | 154/87 (target: | Reduced risk for diabetes related any end points risk by 24% with active control |
| Control: 160/94 | Deaths related to diabetes risk by 32%, stroke risk by 44%, and heart failure risk by 56% | |||||
| Microvascular end points risk by 37% | ||||||
| No benefit in all-cause mortality | ||||||
| HOT, 1998 [24] | 18,790 Hypertensive participants including 1,501 with T2DM | Mean 3.8 yr | 170/105 | DBP: 81.1 in target DBP ≤80 | DBP: 85.2 in target DBP ≤90 | No benefit in CV event in overall participants |
| DBP: 83.2 in target DBP ≤85 | In participants with diabetes, increased major CV event risk by 2.06-fold in target DBP ≤90 compared with ≤80; Increased CV mortality risk by 3.0-fold in target DBP ≤90 compared with ≤80 | |||||
| ADVANCE, 2007 [25] | 11,140 With T2DM aged with 55 yr and older with prior CVD or CV risk factors | Mean 4.3 yr | Active: 145/81 | 136/73 | 140/73 | Reduced risk of major macrovascular or microvascular event by 9%, death from CV disease by 18%, death from any cause by 14% |
| Control: 145/81 | ||||||
| Subgroup analysis of INVEST, 2010 [26] | 6,400 Participants of the 22,576 participants in INVEST aged at least 50 yr with T2DM and CAD | 16,893 Patient-yr | Active: 144/85 | Active SBP: 121.5 (SBP category <130) | Uncontrolled: SBP 146.1 (SBP category ≥140) | No benefit in adverse CV outcome including all-cause death, nonfatal myocardial infarction, or nonfatal stroke in active control of SBP compared with usual control |
| Usual: 149/85 | Usual SBP 131.2 (SBP category 130–140) | Increased risk of adverse CV outcome in uncontrolled SBP group compared with usual control by 1.46-fold | ||||
| Uncontrolled: 159/86 | Increased risk of all-cause mortality in active control compared with usual control by 1.15-fold when extended follow-up | |||||
| ACCORD-BP, 2010 [20] | 4,733 Participants with T2DM aged 40–79 yr with prior CVD or 55–79 yr with CV risk factors | Mean 4.7 yr | Active: 139.0/75.9 | 119.3/64.4 (target SBP: <120) | 135/70.5 (target SBP: 130–140) | No benefit in primary composite outcome including nonfatal MI, nonfatal stroke, and CV death |
| Control: 139.4/76.0 | Reduced risk of stroke by 41% with active control | |||||
| SAEs more common in intensive group, particularly hypotension, elevated serum creatinine and electrolyte imbalance | ||||||
| SPRINT-eligible ACCORD-BP, 2017 [23] | SPRINT-eligible 1,284 participants of the 4,733 participants in ACCORD-BP aged at least 75 yr with T2DM or clinical CVD or subclnical CVD or high CV risk | - | Active: 139.8 | SBP: 120.1 (target SBP: <120) | SBP: 133.5 (target SBP: <140) | Reduced risk of composite of CV death, nonfatal MI, nonfatal stroke, any revascularization, and HF by 21% |
| Control: 140.8 | Reduced risk of CV death, nonfatal MI, and nonfatal stroke by 31% | |||||
| More frequent treatment-related adverse events in active control |
BP, blood pressure; UKPDS, UK Prospective Diabetes Study; T2DM, type 2 diabetes mellitus; HOT, Hypertension Optimal Treatment trial; DBP, diastolic blood pressure; CV, cardiovascular; ADVANCE, Action in Diabetes and Vascular Disease: preterAx and diamicroN-MR Controlled Evaluation trial; CVD, cardiovascular disease; INVEST, International Verapamil SR-Trandolapril Study; CAD, coronary artery disease; SBP, systolic blood pressure; ACCORD-BP, Action to Control Cardiovascular Risk in Diabetes Blood Pressure Trial; MI, myocardial infarction; SAE, serious adverse event; SPRINT, Systolic Blood Pressure Intervention Trial; HF, heart failure.
The Action in Diabetes and Vascular Disease: preterAx and diamicroN-MR Controlled Evaluation trial (ADVANCE) [25] presented BP control goals in patients with diabetes mellitus who experience prior CVD or CV risk factors, providing evidence for setting target BP goals in high-risk patients with diabetes mellitus. This trial showed that the achieved BP was different from 136/73 and 140/73 mm Hg, and that as a result of active control, CV death, all-cause death, and major macrovascular or microvascular complications were significantly reduced. Although this was a trial emphasizing the importance of aggressively active BP control up to 130 mm Hg in patients with CVD or high CV risk, this was not direct evidence because it was a study comparing fixed perindopril-indapamide and placebo in patients with diabetes mellitus, and not comparing target BP itself.
A study reporting the clinical outcome according to the target BP in patients with diabetes mellitus who experience a high CV risk was also presented in a subgroup analysis of the International Verapamil SR-Trandolapril Study (INVEST) in 2010 [26]. The subjects were patients with diabetes mellitus and CAD, the achieved SBP of the group with SBP category of ≥140 mm Hg was 146.1 mm Hg, and the risk of adverse CV events was significantly increased compared to the group with an SBP of 131.2 mm Hg and SBP category of 130 to 140 mm Hg. However, the active control group with SBP
The ACCORD-BP trial [20] is a landmark trial that evaluated the benefits and risks of intensive BP control in patients with type 2 diabetes mellitus and is a pivotal study in several guidelines for BP control in patients with diabetes mellitus. This study also suggests a target BP in patients with diabetes mellitus who experience high CV risk and are aged 40 to 79 years with prior CVD or 55 to 79 years with CV risk factors; therefore, caution is needed in interpretation. In these high-risk patients with diabetes mellitus, adjusting the SBP to
Hypertension and type 2 diabetes mellitus often coexist, and the presence of either of these risk factors increases the risk of CVD. Uncontrolled high BP is an important risk factor for CVD in patients with diabetes mellitus and leads to poor clinical outcomes. However, the optimal target BP in patients with diabetes mellitus has been debated.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
FUNDING
This study was supported by a research grant from the Korea National Institute of Health (grant number: 2021-ER0901, 2021–2023).
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