
==== Front
Sci Rep
Sci Rep
Scientific Reports
2045-2322
Nature Publishing Group UK London

71060
10.1038/s41598-024-71060-8
Article
Association of office blood pressure with ischemic and bleeding events in patients undergoing percutaneous coronary intervention
Kim Byung Sik 1
Shin Jeong-Hun 1
Kim Woohyeun 2
Kook Hyungdon 2
Lee Yonggu 1
Park Jin-Kyu 2
Shin Jinho 2
Lim Young-Hyo mdoim@hanyang.ac.kr

2
1 grid.412145.7 0000 0004 0647 3212 Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Hanyang University Guri Hospital, Guri, Republic of Korea
2 grid.49606.3d 0000 0001 1364 9317 Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Hanyang University Seoul Hospital, 222 Wangsimni-ro, Sungdong-gu, Seoul, 04763 Republic of Korea
2 9 2024
2 9 2024
2024
14 203105 3 2024
23 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Optimal blood pressure (BP) for patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. This study aims to identify the optimal BP by investigating the association between average office BP and future clinical events in patients undergoing PCI. Consecutive patients undergoing PCI from 2012 to 2016 were included. They were divided into five groups according to the average follow-up BP after discharge. The co-primary outcomes were net adverse clinical events (NACE) and major adverse cardiac and cerebrovascular events (MACCE) up to 5 years. NACE was defined as a composite of MACCE (all-cause death, non-fatal myocardial infarction (MI), non-fatal stroke, or any revascularization) or major bleeding. A total of 2845 patients were included, and among them, 787 (27.7%) experienced the NACE during the follow-up period. Patients in the highest SBP group (adjusted hazard ratio [HR] 1.495, confidence interval [CI] 1.189–1.880) and lowest SBP group (adjusted HR 1.625, CI 1.214–2.176) had a significantly higher risk of 5-year NACE. Similar associations were observed between SBP and the risk of MACCE, and similar results based on DBP categories were also observed. There was a J-curve relationship between SBP and DBP with respect to 5-year NACE and MACCE. The nadir point of risk for NACE and MACCE was found at 121.4/74.8 and 120.4/73.7 mmHg. In patients underwent PCI, there is a significant correlation between office BP level and clinical events, indicates the importance of efforts for optimal BP control to reduce ischemic and bleeding events.

Trial registration: HanYang University Medical Center (HYUMC) Registry, NCT05935397.

Keywords

Blood pressure
Coronary artery disease
Hypertension
Percutaneous coronary intervention
Subject terms

Cardiology
Interventional cardiology
issue-copyright-statement© Springer Nature Limited 2024
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pmcIntroduction

Coronary artery disease (CAD) is the main cause of death globally, and accounting for > 9 million deaths in 20171. Percutaneous coronary interventions (PCI) have increasingly been performed for revascularization in patients with CAD and have become the standard treatment in acute coronary syndrome2. Revascularization had advanced in not only procedural aspect, but also aspect of medical treatment3,4. However, the incidence of death or cardiovascular events after revascularization is still high with a 24 to 30% event rate at 10 years5,6. To mitigate these risks of adverse events following revascularization, effective secondary prevention strategies are essential, including lifestyle management, antiplatelet therapy, and treatments for hypertension, dyslipidemia, and diabetes.

There are strong epidemiological relationships between high blood pressure (BP) and CAD7. Despite hypertension being a major modifiable risk factor for CAD8, the optimal BP target for patients with CAD remains unclear. Clinical guidelines for the hypertension recommending a BP target of below 130 mmHg for the systolic blood pressure (SBP) and below 80 mmHg for the diastolic blood pressure (DBP) levels9–11. However, the basis for these recommendations relies on studies conducted primarily on hypertensive patients, including some who also have CAD. Particularly, there is a notable lack of evidence regarding patients who have undergone PCI12. In addition, there have also been reports of a J- or U-curve association between BP and risk of adverse cardiovascular events, suggesting that excessive low BP (particularly < 110/70 or 120/70 mmHg) may be dangerous in patients with CAD13,14. Therefore, this study aimed to identify the optimal BP target by investigating the association between average follow-up office BP and future adverse clinical events after PCI in patients with CAD.

Methods

Study participants

We used data from the HanYang University Medical Center (HYUMC) registry (NCT05935397), an observational, two-center database including consecutive patients with CAD who underwent PCI between 2012 and 2016 at the Division of Cardiology of Hanyang University Seoul Hospital and Hanyang University Guri Hospital in Korea. Consecutive patients treated with one or more drug-eluting stents (DES) at each hospital were eligible for inclusion, irrespective of patient characteristics or lesion complexity.

We reviewed the medical records of 3525 patients and applied the following exclusion criteria: duplicate patients, patients who died during the index hospitalization, patients who were treated with first-generation DES, patients lost to follow-up within 6 months, and patients with insufficient medical records. Finally, the study included 2845 patients who received PCI. Patients were classified according to average office SBP and DBP measured at the outpatient department during the follow-up period after PCI (Fig. 1).Fig. 1 Flow diagram of the study. CAD, coronary artery disease; PCI, percutaneous coronary intervention; DES, drug-eluting stent; SBP, systolic blood pressure.

Data collection

All data were collected from electronic medical records by experienced investigators under the supervision of the principal investigator. Demographic and clinical characteristics, traditional cardiovascular risk factors and comorbidity were obtained. Medication records were collected at the time of discharge, including antiplatelet drugs, anticoagulants, statins, nitrates, angiotensin blockades, β-blockers, calcium channel blockers, diuretics, and mineralocorticoid receptor antagonists.

The following laboratory data were collected: creatinine, fasting glucose, hemoglobin A1c, lipid profiles, and cardiac troponin-I levels. Moreover, the angiographic data were obtained. The left ventricular ejection fraction (LVEF) measured through transthoracic echocardiography performed during the index hospitalization was also acquired.

Patient management and clinical follow-up

Patients were treated in accordance with the standard practices at the respective hospitals. Based on the guidelines, the operator decided on the treatment strategy, including stent implantation and medication selection3. Patients were followed up clinically for 1 month after the procedure and every 3 subsequent months. During outpatient visits, BP measurements were taken using an automated BP machine, OMRON HEM-907XL (OMRON, Kyoto, Japan), after 5 min of quiet rest on seated position. All available office BP readings from the outpatient records were compiled, spanning up to 5 years or including the initial 20 readings following discharge. Average SBP and DBP values were calculated from the obtained SBP and DBP data for subsequent analysis.

Outcome definitions

The co-primary outcomes in this study were net adverse clinical events (NACE) and major adverse cardiac and cerebrovascular events (MACCE) up to 5 years. NACE was defined as a composite of MACCE or major bleeding and MACCE as a composite of all-cause death, non-fatal myocardial infarction (MI), non-fatal stroke, or any revascularization. The secondary outcomes included each component of the primary outcomes.

Clinical outcomes were defined based on the Academic Research Consortium recommendations15. MI was defined as the presence of clinical symptoms accompanied by electrocardiographic changes or imaging evidence indicating new loss of viable myocardium or new regional wall motion abnormalities, including elevated levels of cardiac biomarkers above the 99th percentile upper reference limit. Peri-procedural MI was excluded. Stroke was defined as a neurological deficit resulting from acute focal damage to the central nervous system due to a vascular cause, requiring hospitalization and confirmed by a neurologist through imaging findings. Any revascularization included PCI or coronary artery bypass surgery on either target or non-target vessels. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding16.

Statistical analysis

Categorical variables are reported as frequencies and percentages, while continuous variables are presented as means with standard deviations or medians with interquartile ranges (IQR), depending on their distribution. The distribution of continuous variables was evaluated using the Kolmogorov–Smirnov test and Q-Q plots for visual inspection. Differences between groups were assessed using the chi-square test for categorical variables and one-way analysis of variance (ANOVA) or the Kruskal–Wallis test for continuous variables.

Cumulative event rates were estimated with the Kaplan–Meier curve and compared using the log-rank test. Using a Cox proportional hazard regression model, we calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) for the clinical outcomes according to the BP categories. Multivariable Cox proportional hazard models were conducted adjusting for clinically relevant variables such as age, sex, body mass index, MI presentation, current smoking, hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, previous PCI, previous stroke, LVEF, troponin-I, estimated glomerular filtration rate (eGFR), multivessel disease, and use of anticoagulants, statins, angiotensin blockades, and β-blockers. Subsequently, reduced models were constructed through a backward elimination procedure using the best Akaike’s information criterion. The associations between BP as a continuous variable and the risks of clinical outcomes were assessed by fitting them with a restricted cubic spline curve featuring five knots. Additionally, a sensitivity analysis was performed by excluding the 735 patients who were lost to follow-up and analyzing the hazard ratios of clinical outcomes according to SBP groups for the remaining 2110 patients.

All statistical analyses were conducted using the open-source statistical software R (version 4.3.1, www.R-project.org) and R-studio (version 2023.06.2, www.rstudio.com) and statistical packages, including rms, descr, survival, tableone, survminer, ggplot2, forestploter, and plotRCS. All tests were 2-sided, and P-value of < 0.05 was considered statistically significant.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki and was reviewed and approved by the Institutional Review Board of Hanyang University Seoul Hospital (No. 2022-06-064) and Hanyang University Guri Hospital (No. 2022-06-010). Patient consent is not applicable to this article as it involves a retrospective cohort analysis of deidentified data. The Institutional Review Board waived the need for written informed consent.

Results

Baseline characteristics

Baseline characteristics according to systolic and diastolic BP categories are demonstrated in Table 1 and Supplementary Table 1, respectively. Patients in the higher SBP groups tended to be older, have higher body mass index values, and exhibited a higher prevalence of comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, previous PCI, and previous stroke. Conversely, patients in the lower SBP groups were more likely to be male, had a higher rate of current smoking, and more frequently presented with MI (Table 1).Table 1 Baseline characteristics according to systolic blood pressure categories.

	All patients (n = 2845)	Systolic blood pressure (mmHg)	P-value	
< 110 (n = 158)	110–119 (n = 605)	120–129 (n = 1128)	130–139 (n = 664)	 ≥ 140 (n = 290)	
Age, years	64.79 ± 11.99	64.45 ± 11.24	63.43 ± 11.69	63.75 ± 11.81	66.54 ± 11.95	67.79 ± 12.89	< 0.001	
Men, n (%)	1949 (68.5)	127 (80.4)	425 (70.2)	818 (72.5)	412 (62.0)	167 (57.6)	< 0.001	
Body mass index, kg/m2	24.88 ± 3.39	23.70 ± 3.05	24.46 ± 3.18	25.00 ± 3.37	25.36 ± 3.25	24.87 ± 4.06	< 0.001	
Average follow-up BP, mmHg	
 Systolic BP	126.45 ± 11.37	104.98 ± 4.63	115.66 ± 2.72	125.05 ± 2.77	134.17 ± 2.84	148.48 ± 8.29	< 0.001	
 Diastolic BP	73.01 ± 7.39	63.16 ± 5.54	68.91 ± 5.20	73.22 ± 5.88	75.61 ± 6.67	80.16 ± 8.51	< 0.001	
Index presentation with AMI, n (%)	1175 (41.3)	91 (57.6)	260 (43.0)	467 (41.4)	246 (37.0)	111 (38.3)	0.001	
Risk factors, n (%)	
 Current smoking	816 (28.7)	54 (34.2)	202 (33.4)	342 (30.3)	148 (22.3)	70 (24.1)	< 0.001	
 Hypertension	1693 (59.5)	50 (31.6)	248 (41.0)	652 (57.8)	498 (75.0)	245 (84.5)	< 0.001	
 Diabetes mellitus	986 (34.7)	43 (27.2)	197 (32.6)	351 (31.1)	247 (37.2)	148 (51.2)	< 0.001	
 Dyslipidemia	1135 (39.9)	63 (39.9)	235 (38.8)	466 (41.3)	273 (41.1)	98 (33.9)	0.203	
 Chronic kidney disease	163 (5.7)	7 (4.4)	27 (4.5)	43 (3.8)	36 (5.4)	50 (17.2)	< 0.001	
 Previous PCI	359 (12.6)	18 (11.4)	72 (11.9)	126 (11.2)	105 (15.8)	38 (13.1)	0.066	
 Previous stroke	276 (9.7)	8 (5.1)	55 (9.1)	96 (8.5)	67 (10.1)	50 (17.2)	< 0.001	
Laboratory findings	
 LVEF, %	56.61 ± 11.29	51.56 ± 12.37	56.18 ± 11.16	57.01 ± 11.24	57.94 ± 10.75	55.65 ± 11.56	< 0.001	
 Troponin-I	20 (10, 210)	40 (10, 1100)	20 (10, 230)	20 (10, 180)	20 (10, 150)	40 (10, 250)	0.001a	
 eGFR, mL/min/1.73 m2	80.34 ± 24.12	81.93 ± 21.89	83.32 ± 21.46	83.96 ± 21.52	77.64 ± 24.55	65.35 ± 31.66	< 0.001	
 Total cholesterol, mg/dL	168 (141, 200)	167 (140, 203)	165 (136, 196)	170 (144, 201)	169 (144, 201)	164 (135, 198)	0.057a	
 LDL cholesterol, mg/dL	99 (77, 125)	103 (77, 131)	98 (74, 123)	101 (77, 125)	100 (79, 123)	98 (74, 127)	0.490a	
 HDL cholesterol, mg/dL	41 (35, 48)	41 (34, 49)	41 (35, 48)	41 (34, 48)	41 (35, 48)	41 (34, 48)	0.975a	
 Triglyceride, mg/dL	122 (87, 178)	121 (85, 154)	121 (84, 174)	123 (89, 183)	125 (89, 182)	115 (81, 171)	0.056a	
 HbA1c, %	5.9 (5.5, 6.6)	5.8 (5.5, 6.2)	5.8 (5.5, 6.6)	5.8 (5.5, 6.5)	5.9 (5.6, 6.6)	6.0 (5.5, 7.1)	0.006a	
Procedural characteristics	
 Multivessel disease, n (%)	1048 (36.8)	49 (31.0)	202 (33.4)	436 (38.7)	243 (36.6)	118 (40.7)	0.065	
 Target lesion, n (%)	
  Left main coronary artery	71 (2.5)	4 (2.5)	20 (3.3)	21 (1.9)	16 (2.4)	10 (3.4)	0.331	
  Left anterior descending artery	1922 (67.6)	104 (65.8)	405 (66.9)	772 (68.4)	433 (65.2)	208 (71.7)	0.321	
  Left circumflex artery	981 (34.5)	52 (32.9)	191 (31.6)	395 (35.0)	242 (36.4)	101 (34.8)	0.443	
  Right coronary artery	1167 (41.0)	56 (35.4)	240 (39.7)	470 (41.7)	280 (42.2)	121 (41.7)	0.541	
 Chronic total occlusion, n (%)	199 (7.0)	11 (7.0)	34 (5.6)	90 (8.0)	42 (6.3)	22 (7.6)	0.399	
 In-stent restenosis, n (%)	120 (4.2)	5 (3.2)	22 (3.6)	45 (4.0)	39 (5.9)	9 (3.1)	0.167	
 Discharge medication, n (%)								
 Aspirin	2795 (98.2)	157 (99.4)	592 (97.9)	1107 (98.1)	653 (98.3)	286 (98.6)	0.728	
Type of P2Y12 inhibitor	
  Clopidogrel	1910 (67.1)	88 (55.7)	365 (60.3)	768 (68.1)	475 (71.5)	214 (73.8)	< 0.001	
  Ticagrelor	638 (22.4)	52 (32.9)	156 (25.8)	245 (21.7)	128 (19.3)	57 (19.7)	0.001	
  Prasugrel	214 (7.5)	17 (10.8)	67 (11.1)	80 (7.1)	42 (6.3)	8 (2.8)	< 0.001	
 Cilostazol	365 (12.8)	23 (14.6)	68 (11.2)	152 (13.5)	78 (11.7)	44 (15.2)	0.363	
 Anti-coagulant	48 (1.7)	1 (0.6)	10 (1.7)	25 (2.2)	6 (0.9)	6 (2.1)	0.224	
 Statin	2617 (92.0)	146 (92.4)	567 (93.7)	1045 (92.6)	606 (91.3)	253 (87.2)	0.014	
 Nitrate	1675 (58.9)	70 (44.3)	323 (53.4)	685 (60.7)	416 (62.7)	181 (62.4)	< 0.001	
 Angiotensin blockade	1633 (57.4)	92 (58.2)	354 (58.5)	615 (54.5)	387 (58.3)	185 (63.8)	0.056	
 Beta-blocker	2018 (70.9)	120 (75.9)	427 (70.6)	791 (70.1)	467 (70.3)	213 (73.4)	0.504	
 Calcium channel blocker	341 (12.0)	8 (5.1)	61 (10.1)	114 (10.1)	92 (13.9)	66 (22.8)	< 0.001	
 Diuretics	478 (16.8)	49 (31.0)	107 (17.7)	168 (14.9)	94 (14.2)	60 (20.7)	< 0.001	
 MRA	334 (11.7)	39 (24.7)	81 (13.4)	125 (11.1)	62 (9.3)	27 (9.3)	< 0.001	
Data are presented as n (%) or median (interquartile range). BP, blood pressure; AMI, acute myocardial infarction; PCI, percutaneous coronary intervention; LVEF, left ventricular ejection fraction; eGFR, estimated glomerular filtration rate; LDL, low-density lipoprotein; HDL, high-density lipoprotein; MRA, mineralocorticoid receptor antagonist.

aAs assessed using nonparametric tests.

Contrastingly, patients in the lower DBP groups were more likely to be older, female, leaner and had a higher prevalence of diabetes mellitus, while those in the higher DBP groups had a higher rate of current smoking and a greater prevalence of hypertension and dyslipidemia (Supplementary Table 1). However, the angiographic characteristics were similar across all groups.

Clinical outcomes

The median duration of follow-up was 5.43 (IQR: 2.05–8.42) years, and the median number of BP readings was 20 (IQR: 10–20). During the follow-up period, NACE and MACCE occurred in 787 (27.7%) and 559 (19.6%) patients, respectively. Kaplan–Meier curves for the incidence rates of the primary and secondary outcomes according to SBP and DBP categories are presented in Figs. 2 and 3. The incidence rates of NACE and MACCE were highest in patients with the highest SBP (≥ 140 mmHg), followed by patients with the lowest SBP (< 110 mmHg), while the remaining patients exhibited similar incidence rates. A similar trend was observed for the other secondary outcomes, excluding any revascularization (Fig. 2 and Table 2).Fig. 2 Kaplan–Meier curves for the cumulative incidence of the clinical outcomes according to SBP categories. (A) NACE, (B) MACCE, (C) all-cause death, (D) major bleeding, (E) non-fatal myocardial infarction, (F) non-fatal stroke, and (G) any revascularization. NACE, net adverse clinical events; MACCE, major adverse cardiac and cerebrovascular events; SBP, systolic blood pressure.

Fig. 3 Kaplan–Meier curves for the cumulative incidence of the clinical outcomes according to DBP categories. (A) NACE, (B) MACCE, (C) all-cause death, (D) major bleeding, (E) non-fatal myocardial infarction, (F) non-fatal stroke, and (G) any revascularization. NACE, net adverse clinical events; MACCE, major adverse cardiac and cerebrovascular events; DBP, diastolic blood pressure.

Table 2 Incidences and hazard ratios for the primary and secondary outcomes according to systolic blood pressure.

	Cumulative incidence (%)	Univariable analysis	Multivariable analysisa	
Hazard ratio (95% CI)	P-value	Hazard ratio (95% CI)	P-value	
NACEa	
 SBP < 110	57/158 (36.1)	1.695 (1.274–2.255)	< 0.001	1.625 (1.214–2.176)	0.001	
 SBP 110–119	156/605 (25.8)	1.091 (0.896–1.328)	0.387	1.131 (0.927–1.380)	0.226	
 SBP 120–129	271/1128 (24.0)	Reference		Reference		
 SBP 130–139	181/664 (27.3)	1.178 (0.976–1.422)	0.088	1.077 (0.888–1.306)	0.453	
 SBP ≥ 140	122/290 (42.1)	2.177 (1.758–2.696)	< 0.001	1.495 (1.189–1.880)	0.001	
MACCEc	
 SBP < 110	41/158 (25.9)	1.710 (1.221–2.396)	0.002	1.642 (1.166–2.311)	0.005	
 SBP 110–119	102/605 (16.9)	0.991 (0.780–1.260)	0.944	0.993 (0.780–1.266)	0.957	
 SBP 120–129	193/1128 (17.1)	Reference		Reference		
 SBP 130–139	117/664 (17.6)	1.047 (0.833–1.318)	0.692	0.983 (0.779–1.242)	0.888	
 SBP ≥ 140	106/290 (36.6)	2.639 (2.082–3.346)	< 0.001	2.053 (1.598–2.637)	< 0.001	
All-cause death	
 SBP < 110	20/158 (12.7)	2.895 (1.735–4.830)	< 0.001	2.941 (1.744–4.961)	< 0.001	
 SBP 110–119	19/605 (3.1)	0.642 (0.381–1.082)	0.096	0.619 (0.363–1.056)	0.078	
 SBP 120–129	55/1128 (4.9)	Reference		Reference		
 SBP 130–139	26/664 (3.9)	0.817 (0.512–1.302)	0.395	0.647 (0.400–1.046)	0.076	
 SBP ≥ 140	65/290 (22.4)	5.780 (4.034–8.282)	< 0.001	3.540 (2.399–5.221)	< 0.001	
Major bleedingd	
 SBP < 110	31/158 (19.6)	1.992 (1.343–2.955)	0.001	1.854 (1.237–2.780)	0.003	
SBP 110–119	79/605 (13.1)	1.225 (0.923–1.626)	0.159	1.294 (0.971–1.724)	0.079	
 SBP 120–129	122/1128 (10.8)	Reference		Reference		
 SBP 130–139	100/664 (15.1)	1.444 (1.108–1.881)	0.006	1.207 (0.919–1.586)	0.175	
 SBP ≥ 140	60/290 (20.7)	2.371 (1.740–3.230)	< 0.001	1.313 (0.942–1.829)	0.108	
Non-fatal MI	
 SBP < 110	8/158 (5.1)	2.255 (1.031–4.934)	0.042	1.891 (0.859–4.159)	0.113	
 SBP 110–119	19/605 (3.1)	1.226 (0.687–2.186)	0.491	1.143 (0.634–2.059)	0.656	
 SBP 120–129	29/1128 (2.6)	Reference		Reference		
 SBP 130–139	22/664 (3.3)	1.310 (0.753–2.281)	0.339	1.267 (0.727–2.207)	0.404	
 SBP ≥ 140	16/290 (5.5)	2.711 (1.471–4.994)	0.001	2.147 (1.134–4.065)	0.019	
Non-fatal stroke	
 SBP < 110	7/158 (4.4)	2.517 (1.076–5.887)	0.033	2.636 (1.048–6.632)	0.040	
SBP 110–119	9/605 (1.5)	0.762 (0.351–1.655)	0.492	0.821 (0.376–1.793)	0.621	
 SBP 120–129	22/1128 (2.0)	Reference		Reference		
 SBP 130–139	11/664 (1.7)	0.864 (0.419–1.782)	0.692	0.821 (0.393–1.715)	0.599	
 SBP ≥ 140	19/290 (6.6)	4.084 (2.208–7.553)	< 0.001	3.216 (1.665–6.212)	0.001	
Any revascularization	
 SBP < 110	17/158 (10.8)	1.024 (0.618–1.697)	0.928	1.032 (0.621–1.716)	0.268	
 SBP 110–119	79/605 (13.1)	1.133 (0.857–1.498)	0.381	1.131 (0.853–1.499)	0.393	
 SBP 120–129	131/1128 (11.6)	Reference		Reference		
 SBP 130–139	88/664 (13.3)	1.161 (0.886–1.521)	0.280	1.118 (0.852–1.466)	0.423	
 SBP ≥ 140	41/290 (14.1)	1.486 (1.046–2.110)	0.027	1.206 (0.829–1.753)	0.327	
NACE, net adverse clinical events; MACCE, major adverse cardiac and cerebrovascular events; SBP, systolic blood pressure; MI, myocardial infarction; CI, confidence interval.

aAdjustment for age, sex, body mass index, presentation with MI, current smoking, hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, previous PCI, previous stroke, left ventricular ejection fraction, troponin-I, estimated glomerular filtration rate, multivessel disease, and use of anticoagulants, statins, angiotensin blockades, and β-blockers.

bNACE was defined as a composite of all-cause death, non-fatal MI, non-fatal stroke, any revascularization, or major bleeding.

cMACCE was defined as a composite of all-cause death, non-fatal MI, non-fatal stroke, or any revascularization.

dMajor bleeding was defined as Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding.

Regarding the incidence rates of the primary and secondary outcomes according to DBP categories, the highest rates of MACCE, all-cause death, non-fatal MI, and any revascularization were observed in the highest DBP group (≥ 90 mmHg), followed by the lowest DBP group (< 60 mmHg). The incidence rate of NACE and non-fatal stroke was highest in the lowest DBP group, followed by the highest DBP group. Additionally, the incidence rate of major bleeding was highest in the lowest DBP group, and there was a decreasing trend in the incidence rate as the DBP increased (Fig. 3 and Table 3).Table 3 Incidences and hazard ratios for the primary and secondary outcomes according to diastolic blood pressure.

	Cumulative incidence	Univariable analysis	Multivariable analysisa	
Hazard ratio (95% CI)	P-value	Hazard ratio (95% CI)	P-value	
NACEb	
 DBP < 60	57/114 (50.0)	2.816 (2.127–3.728)	< 0.001	2.038 (1.525–2.724)	< 0.001	
 DBP 60–69	265/814 (32.6)	1.477 (1.258–1.734)	< 0.001	1.268 (1.074–1.496)	0.005	
 DBP 70–79	341/1465 (23.3)	Reference		Reference		
 DBP 80–89	107/416 (41.6)	1.224 (0.985–1.521)	0.069	1.369 (1.097–1.708)	0.005	
 DBP ≥ 90	17/36 (47.2)	2.310 (1.419–3.759)	0.001	2.794 (1.685–4.633)	< 0.001	
MACCEc	
 DBP < 60	36/114 (31.6)	2.285 (1.609–3.245)	< 0.001	1.827 (1.277–2.613)	0.001	
 DBP 60–69	179/814 (22.0)	1.404 (1.156–1.705)	0.001	1.241 (1.017–1.515)	0.033	
 DBP 70–79	238/1465 (16.2)	Reference		Reference		
 DBP 80–89	89/416 (21.4)	1.462 (1.146–1.866)	0.002	1.629 (1.270–2.090)	< 0.001	
 DBP ≥ 90	17/36 (47.2)	3.573 (2.193–5.823)	< 0.001	4.403 (2.638–7.348)	< 0.001	
All-cause death	
 DBP < 60	16/114 (14.0)	2.940 (1.717–5.032)	< 0.001	1.494 (0.859–2.598)	0.155	
 DBP 60–69	45/814 (5.5)	1.037 (0.719–1.495)	0.847	0.728 (0.497–1.066)	0.102	
 DBP 70–79	79/1465 (5.4)	Reference		Reference		
 DBP 80–89	38/416 (9.1)	1.897 (1.288–2.794)	0.001	2.557 (1.708–3.828)	< 0.001	
 DBP ≥ 90	7/36 (19.4)	4.394 (2.030–9.511)	< 0.001	7.817 (3.526–17.326)	< 0.001	
Major bleedingd	
 DBP < 60	39/114 (34.2)	3.788 (2.671–5.371)	< 0.001	2.140 (1.484–3.084)	< 0.001	
 DBP 60–69	141/814 (17.3)	1.580 (1.262–1.977)	< 0.001	1.245 (0.987–1.571)	0.064	
 DBP 70–79	166/1465 (11.3)	Reference		Reference		
 DBP 80–89	43/416 (10.3)	1.008 (0.720–1.409)	0.964	1.184 (0.841–1.666)	0.334	
 DBP ≥ 90	3/36 (8.3)	0.829 (0.265–2.598)	0.748	1.155 (0.367–3.638)	0.805	
Non-fatal MI	
 DBP < 60	7/114 (6.1)	2.812 (1.253–6.308)	0.012	2.678 (1.191–6.023)	0.017	
 DBP 60–69	31/814 (3.8)	1.535 (0.953–2.474)	0.078	1.411 (0.869–2.290)	0.164	
 DBP 70–79	37/1465 (2.5)	Reference		Reference		
 DBP 80–89	14/416 (3.4)	1.493 (0.807–2.762)	0.201	1.359 (0.722–2.558)	0.342	
 DBP ≥ 90	5/36 (13.9)	6.844 (2.690–17.411)	< 0.001	6.840 (2.679–17.467)	< 0.001	
Non-fatal stroke	
 DBP < 60	7/114 (6.1)	3.714 (1.617–8.531)	0.002	2.116 (0.885–5.059)	0.092	
 DBP 60–69	18/814 (2.2)	1.215 (0.669–2.205)	0.523	0.972 (0.528–1.789)	0.928	
 DBP 70–79	27/1465 (1.8)	Reference		Reference		
 DBP 80–89	14/416 (3.4)	2.021 (1.059–3.854)	0.033	2.498 (1.293–4.826)	0.006	
 DBP ≥ 90	2/36 (5.6)	3.590 (0.853–15.099)	0.081	5.385 (1.249–23.218)	0.024	
Any revascularization	
 DBP < 60	18/114 (15.8)	1.710 (1.050–2.786)	0.031	1.815 (1.107–2.974)	0.018	
 DBP 60–69	127/814 (15.6)	1.509 (1.194–1.907)	.001	1.527 (1.203–1.937)	< .001	
 DBP 70–79	156/1465 (10.6)	Reference		Reference		
 DBP 80–89	45/416 (10.8)	1.119 (0.803–1.560)	0.506	1.100 (0.786–1.540)	0.578	
 DBP ≥ 90	10/36 (27.8)	3.203 (1.695–6.053)	< 0.001	3.001 (1.528–5.893)	0.001	
NACE, net adverse clinical events; MACCE, major adverse cardiac and cerebrovascular events; SBP, systolic blood pressure; MI, myocardial infarction; CI, confidence interval.

aAdjustment for age, sex, body mass index, presentation with MI, current smoking, hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, previous PCI, previous stroke, left ventricular ejection fraction, troponin-I, estimated glomerular filtration rate, multivessel disease, anticoagulant, statin, angiotensin blockade, and β-blockers.

bNACE was defined as a composite of all-cause death, non-fatal MI, non-fatal stroke, any revascularization, or major bleeding.

cMACCE was defined as a composite of all-cause death, non-fatal MI, non-fatal stroke, or any revascularization.

dMajor bleeding was defined as Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding.

Tables 2 and 3 present the incidence rates of the primary and secondary outcomes and the corresponding HR for these outcomes, using the reference intervals of 120–129 mmHg for SBP and 70–79 mmHg for DBP. After adjusting for the clinically relevant covariates, the highest SBP (adjusted HR 1.495, CI 1.189–1.880 for NACE and adjusted HR 2.053, CI 1.598–2.637 for MACCE) and lowest SBP groups (adjusted HR 1.625, CI 1.214–2.176 for NACE and adjusted HR 1.642, CI 1.166–2.311 for MACCE) demonstrated a significantly higher risk of 5-year NACE, MACCE, all-cause death, and non-fatal stroke. The highest SBP group also had a higher risk of 5-year non-fatal MI, while the lowest SBP group had a higher risk of 5-year major bleeding (Table 2 and Supplementary Fig. 1).

The risk of NACE and MACCE according to DBP showed higher HRs in the highest DBP group, lowest DBP group, DBP 80–89 mmHg group, and DBP 60–69 mmHg group compared to the reference group (DBP 70–79 mmHg), and all of these differences were statistically significant. For major bleeding, a significantly higher risk was observed only in the lowest DBP group (Table 3 and Supplementary Fig. 2).

The restrictive cubic spline curves illustrate the continuous relationship between BP and the risk of primary and secondary outcomes (Figs. 4 and 5). The results revealed that SBP exhibited a J- or U-shaped curve in relation to the risk of primary and secondary outcomes. The analysis identified a nadir of 121.4 and 120.4 mmHg for SBP, indicating the point at which the risk of NACE and MACCE was the lowest (Fig. 4). Similarly, DBP followed a J- or U-shaped curve in relation to the risk of primary and secondary outcomes, although it was less pronounced than SBP. The nadir for DBP was found to be 74.8 and 73.7 mmHg, indicating the point at which the risk of NACE and MACCE was the lowest (Fig. 5).Fig. 4 Continuous association between SBP and the risk of clinical outcomes. (A) NACE, (B) MACCE, (C) all-cause death, (D) major bleeding, (E) non-fatal myocardial infarction, (F) non-fatal stroke, and (G) any revascularization. NACE, net adverse clinical events; MACCE, major adverse cardiac and cerebrovascular events; SBP, systolic blood pressure; CI, confidence interval.

Fig. 5 Continuous association between DBP and the risk of clinical outcomes. (A) NACE, (B) MACCE, (C) all-cause death, (D) major bleeding, (E) non-fatal myocardial infarction, (F) non-fatal stroke, and (G) any revascularization. NACE, net adverse clinical events; MACCE, major adverse cardiac and cerebrovascular events; DBP, diastolic blood pressure; CI, confidence interval.

We performed a subgroup analysis stratified by age (< 60, 60–74, or ≥ 75 years), sex, LVEF (≤ 40, 41–49, or ≥ 50%), and eGFR (< 30, 30–59, or ≥ 60 mL/min/1.73 m2). The results showed a J- or U-shaped association in most subgroups, with the lowest risk point of primary and secondary outcomes observed between SBP 120–135 mmHg and DBP 70–80 mmHg. In patients under 60 years, a J- or U-shaped association was observed between DBP and the primary outcome but not for SBP (Supplementary Fig. 3–6). Additionally, a comparison of the baseline characteristics according to dropout status revealed that the groups were largely similar, with the exception of differences in the prevalence of diabetes mellitus and dyslipidemia (Supplementary Table 2). A sensitivity analysis was conducted, excluding the 735 patients who were lost to follow-up. The results were found to be consistent with those of the primary analysis (Supplementary Table 3).

Discussion

This is the first study to demonstrate the long-term association between follow-up BP and adverse clinical events, including ischemic and bleeding events, in patients with CAD who underwent PCI. The key findings of this study were as follows: (1) A strong correlation was found between office BP and 5-year MACCE and NACE. (2) The lowest risk of primary outcomes was associated with a nadir BP point of 121.4/74.8 mmHg for NACE and 120.4/73.7 mmHg for MACCE. (3) A J-shaped relationship was observed, indicating that BP below 110/70 mmHg were associated with an elevated risk of NACE and MACCE. This suggests that excessively low BP may indicate an unfavorable prognosis in patients who underwent PCI.

The optimal BP targets for hypertensive patients with CAD are still a subject of debate, given the limited number of randomized clinical trials specifically addressing this question. A post-hoc analysis of the INternational VErapamil SR Trandolapril STudy (INVEST) suggested that reducing SBP below 140 mmHg may benefit elderly hypertensive patients with CAD17. Similarly, the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) trial observed that the lowest event rates were associated with an SBP range of 130–140 mmHg in patients with acute coronary syndrome14. Additionally, the Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study demonstrated that amlodipine treatment reduced cardiovascular events in normotensive CAD patients18. Furthermore, in a recent post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), positive cardiovascular benefits from intensive BP control were found to be attenuated in patients with CAD compared with those without CAD; however, intensive BP control in CAD patients showed beneficial effects in reducing all-cause mortality. Considering these findings, incorporating CAD patients as high-risk individuals in conjunction with meta-analyses19–22, clinical practice guidelines for hypertension management recommend a BP target of < 130/80 mmHg for hypertensive patients with CAD9–11, even though there have been no specific studies on optimal BP levels for CAD patients.

The evidence supporting the applicability of the same BP target in CAD patients who underwent PCI is even more limited. A previous single-center registry study demonstrated that lower SBP values below 120 mmHg were associated with future cardiovascular benefits23. A recent study utilizing the Korean National Health Insurance System (NHIS) database identified that a nadir BP of 119/74 mmHg was associated with the lowest all-cause mortality in CAD patients who underwent PCI12. Although the study only investigated all-cause mortality and utilized a single measurement of BP, the observed BP nadir in that study closely aligned with the BP nadir observed in our study. In contrast, our study collected follow-up BP measurements in the outpatient department after PCI, allowing us to demonstrate results more reflective of real-world clinical situations.

While the benefits of intensive BP control have been emphasized recently, concerns remain regarding the presence of J-shaped relationships, particularly in CAD patients. Moreover, higher mortality rates and cardiovascular adverse events are associated with high and low SBP and DBP values12–14,24–26. Taking this into consideration, the guidelines recommend not lowering BP below 110 ~ 120/70 mmHg for patients with CAD9,11.

The J-curve phenomenon was more pronounced in DBP, aligning with the rationale that coronary perfusion occurs during diastole27. However, these J-shaped relationships can vary depending on the patient’s revascularization status. A post hoc analysis of the INVEST study revealed that the relationship between DBP and cardiovascular outcomes was J-shaped in PCI patients but not in CABG patients, where it was linear and positive28. In our study, we similarly observed a J-curve phenomenon for SBP and DBP, but it was more pronounced in the SBP curve than in the DBP curve, which may be attributed to the effects of revascularization. Additionally, the relationship between BP and clinical outcomes remained consistent across most subgroups. Notably, although no significant interaction was found, among patients under 60 years of age, SBP did not display a J-curve phenomenon concerning NACE and MACCE. This suggests that situations where SBP is lowered due to medications for other compelling indications might be relatively safe. These novel findings in younger patients warrant further prospective evidence.

Strong evidence supports the use of dual antiplatelet therapy in patients with CAD undergoing PCI4. However, these benefits come with an increased risk of bleeding. Given the significant association between bleeding events and mortality29, efforts have been made identify high-risk groups for bleeding events and to tailor antiplatelet therapy to reduce bleeding events after PCI30,31. The risk of recurrent ischemia and bleeding after PCI varies over time; therefore, optimizing the balance between ischemic and bleeding risk remains a challenge for physicians managing patients undergoing PCI32. BP represents a crucial factor that can be associated with both ischemic and bleeding risks12,33. However, there have been no studies on the association between BP and bleeding events after PCI. In our study, we observed a J-curve relationship between BP and bleeding events in both SBP and DBP. While there are no previous studies with a similar clinical setting, a J-curve association between BP levels and bleeding risk was also observed in patient on long-term anticoagulation treatment34. These findings suggest that patients with low BP may potentially be frailer and, consequently, have a higher risk of experiencing bleeding events. Moreover, low BP might be linked to vascular vulnerability35. Further prospective studies investigating the association between BP and the risk of bleeding are necessary to validate these findings.

Overall, this study holds clinical significance as it provides insights into the importance of intensive BP management and offers clues regarding target BP levels in CAD patients who underwent PCI. It utilizes a large dataset from follow-up BP data from consecutive PCI patients treated with second-generation DES, reflecting real-world clinical scenarios. In addition, this study analyzed the associations between these patients and bleeding events, which has not been thoroughly explored previously. Concerning BP relationship, rather than a trade-off, bleeding events are similarly associated with ischemic events, thus suggesting that appropriately managing BP may be even more critical than expected for patients who underwent PCI, a high-risk group for bleeding and ischemic events simultaneously.

This study had several limitations. First, it was observational in nature, as a consequence, was subject to the inherent limitations associated with such a design. Notwithstanding the rigorous adjustments for the known risk factors, the possibility of unmeasured confounding factors remains. Additionally, the inherent selection bias of observational studies, including patient characteristics and treatment decisions, may have influenced the outcomes. Second, important variables, such as compliance with antiplatelet and antihypertensive agents, familial history of premature atherosclerotic cardiovascular events, socioeconomic status, job stress, mental health, smoking cessation, and other lifestyle factors (e.g., diet, exercise) after PCI, were unavailable for analysis. Furthermore, the impact of alterations in treatment regimens over the course of the follow-up period was not taken into account. These factors are indeed significant and have the potential to influence both BP levels and cardiovascular outcomes, which may in turn affect the results of the study. Moreover, adverse events associated with BP-lowering treatment, such as hypotension, syncope, bradycardia, electrolyte imbalance, and acute kidney injury, were not considered. This is a crucial omission, as it precludes a comprehensive understanding of the full spectrum of risks associated with different BP targets. Third, the data were collected from two PCI centers within the same university medical system in Korea, which may limit the generalizability of our findings to other settings and populations. Therefore, further studies are needed to validate our findings in diverse populations. Fourth, the longitudinal analysis may be influenced by dropouts during the follow-up, introducing potential unknown biases. Finally, although we utilized average follow-up BP measurements, we cannot completely exclude the reverse causality risk. To address these limitations, future randomized controlled trials are necessary to confirm our findings and establish definitive causal relationships.

This study provides valuable insights into the association between follow-up office BP and clinical outcomes in CAD patients who underwent PCI, leveraging a large dataset reflecting real-world clinical scenarios. Although a J-curve relationship was observed between BP and clinical outcomes, the lowest BP nadir associated with the lowest risk of future cardiovascular events in CAD patients who underwent PCI was identified as 121.4/74.8 mmHg for NACE and 120.4/73.7 mmHg for MACCE, indicating the potential benefits of strict BP control strategies. However, further research, including randomized controlled trials, is needed to establish definitive BP targets and optimize cardiovascular outcomes in this specific group of patients.

Supplementary Information

Supplementary Information.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-024-71060-8.

Author contributions

B.S.K. contributed to the acquisition and interpretation of data, and was a major contributor in writing the manuscript. J.-H.S. contributed to the interpretation of data and also was a major contributor in writing the manuscript. W.K. and H.K. contributed to the acquisition and analysis of data. Y.L., J.-K.P., and J.S. provided critical revisions to the manuscript. Y.-H.L. was responsible for study design, data interpretation, and manuscript preparation. All authors read and approved the final manuscript.

Data availability

The datasets generated the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

These authors contributed equally: Byung Sik Kim and Jeong-Hun Shin.
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References

1. Dai H Global, regional, and national burden of ischaemic heart disease and its attributable risk factors, 1990–2017: Results from the Global Burden of Disease Study 2017 Eur. Heart J. Qual. Care Clin. Outcomes 2020 8 50 60 10.1093/ehjqcco/qcaa076
Dai, H. et al. Global, regional, and national burden of ischaemic heart disease and its attributable risk factors, 1990–2017: Results from the Global Burden of Disease Study 2017. Eur. Heart J. Qual. Care Clin. Outcomes 8, 50–60 (2020).10.1093/ehjqcco/qcaa076
2. Tocci G Blood pressure levels at the time of percutaneous coronary revascularization and risk of coronary in-stent restenosis Am. J. Hypertens. 2016 29 509 518 10.1093/ajh/hpv131 26271109
Tocci, G. et al. Blood pressure levels at the time of percutaneous coronary revascularization and risk of coronary in-stent restenosis. Am. J. Hypertens. 29, 509–518 (2016).26271109 10.1093/ajh/hpv131
3. Lawton JS 2021 ACC/AHA/SCAI guideline for coronary artery revascularization J. Am. Coll. Cardiol. 2022 79 e21 e129 10.1016/j.jacc.2021.09.006 34895950
Lawton, J. S. et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization. J. Am. Coll. Cardiol. 79, e21–e129 (2022).34895950 10.1016/j.jacc.2021.09.006
4. Valgimigli M 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS) Eur. Heart J. 2017 39 213 260 10.1093/eurheartj/ehx419
Valgimigli, M. et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 39, 213–260 (2017).10.1093/eurheartj/ehx419
5. Thuijs D Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial Lancet 2019 394 1325 1334 10.1016/S0140-6736(19)31997-X 31488373
Thuijs, D. et al. Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial. Lancet 394, 1325–1334 (2019).31488373 10.1016/S0140-6736(19)31997-X
6. Alkhouli M Trends in characteristics and outcomes of patients undergoing coronary revascularization in the United States, 2003–2016 JAMA Netw. Open 2020 3 e1921326 10.1001/jamanetworkopen.2019.21326 32058558
Alkhouli, M. et al. Trends in characteristics and outcomes of patients undergoing coronary revascularization in the United States, 2003–2016. JAMA Netw. Open 3, e1921326 (2020).32058558 10.1001/jamanetworkopen.2019.21326
7. Yusuf S Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study Lancet 2004 364 937 952 10.1016/S0140-6736(04)17018-9 15364185
Yusuf, S. et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. Lancet 364, 937–952 (2004).15364185 10.1016/S0140-6736(04)17018-9
8. Fuchs FD Whelton PK High blood pressure and cardiovascular disease Hypertension 2020 75 285 292 10.1161/HYPERTENSIONAHA.119.14240 31865786
Fuchs, F. D. & Whelton, P. K. High blood pressure and cardiovascular disease. Hypertension 75, 285–292 (2020).31865786 10.1161/HYPERTENSIONAHA.119.14240
9. Williams B 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) Eur. Heart J. 2018 39 3021 3104 10.1093/eurheartj/ehy339 30165516
Williams, B. et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur. Heart J. 39, 3021–3104 (2018).30165516 10.1093/eurheartj/ehy339
10. Whelton PK 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, Detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines Hypertension 2018 71 e13 e115 29133356
Whelton, P. K. et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, Detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 71, e13–e115 (2018).29133356
11. Kim HL The 2022 focused update of the 2018 Korean hypertension society guidelines for the management of hypertension Clin. Hypertens. 2023 29 11 10.1186/s40885-023-00234-9 36788612
Kim, H. L. et al. The 2022 focused update of the 2018 Korean hypertension society guidelines for the management of hypertension. Clin. Hypertens. 29, 11 (2023).36788612 10.1186/s40885-023-00234-9
12. Lee CW Blood pressure and mortality after percutaneous coronary intervention: A population-based cohort study Sci. Rep. 2022 12 2768 10.1038/s41598-022-06627-4 35177716
Lee, C. W. et al. Blood pressure and mortality after percutaneous coronary intervention: A population-based cohort study. Sci. Rep. 12, 2768 (2022).35177716 10.1038/s41598-022-06627-4
13. Vidal-Petiot E Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: An international cohort study Lancet 2016 388 2142 2152 10.1016/S0140-6736(16)31326-5 27590221
Vidal-Petiot, E. et al. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: An international cohort study. Lancet 388, 2142–2152 (2016).27590221 10.1016/S0140-6736(16)31326-5
14. Bangalore S Qin J Sloan S Murphy SA Cannon CP What is the optimal blood pressure in patients after acute coronary syndromes?: Relationship of blood pressure and cardiovascular events in the PRavastatin OR atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial Circulation 2010 122 2142 2151 10.1161/CIRCULATIONAHA.109.905687 21060068
Bangalore, S., Qin, J., Sloan, S., Murphy, S. A. & Cannon, C. P. What is the optimal blood pressure in patients after acute coronary syndromes?: Relationship of blood pressure and cardiovascular events in the PRavastatin OR atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial. Circulation 122, 2142–2151 (2010).21060068 10.1161/CIRCULATIONAHA.109.905687
15. Garcia-Garcia HM Standardized end point definitions for coronary intervention trials: The academic research consortium-2 consensus document Circulation 2018 137 2635 2650 10.1161/CIRCULATIONAHA.117.029289 29891620
Garcia-Garcia, H. M. et al. Standardized end point definitions for coronary intervention trials: The academic research consortium-2 consensus document. Circulation 137, 2635–2650 (2018).29891620 10.1161/CIRCULATIONAHA.117.029289
16. Mehran R Standardized bleeding definitions for cardiovascular clinical trials: A consensus report from the Bleeding Academic Research Consortium Circulation 2011 123 2736 2747 10.1161/CIRCULATIONAHA.110.009449 21670242
Mehran, R. et al. Standardized bleeding definitions for cardiovascular clinical trials: A consensus report from the Bleeding Academic Research Consortium. Circulation 123, 2736–2747 (2011).21670242 10.1161/CIRCULATIONAHA.110.009449
17. Bangalore S Gong Y Cooper-DeHoff RM Pepine CJ Messerli FH 2014 Eighth Joint National Committee panel recommendation for blood pressure targets revisited: results from the INVEST study J. Am. Coll. Cardiol. 2014 64 784 793 10.1016/j.jacc.2014.05.044 25145522
Bangalore, S., Gong, Y., Cooper-DeHoff, R. M., Pepine, C. J. & Messerli, F. H. 2014 Eighth Joint National Committee panel recommendation for blood pressure targets revisited: results from the INVEST study. J. Am. Coll. Cardiol. 64, 784–793 (2014).25145522 10.1016/j.jacc.2014.05.044
18. Nissen SE Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: A randomized controlled trial JAMA 2004 292 2217 2225 10.1001/jama.292.18.2217 15536108
Nissen, S. E. et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: A randomized controlled trial. JAMA 292, 2217–2225 (2004).15536108 10.1001/jama.292.18.2217
19. Leenen FH Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial Hypertension 2006 48 374 384 10.1161/01.HYP.0000231662.77359.de 16864749
Leenen, F. H. et al. Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial. Hypertension 48, 374–384 (2006).16864749 10.1161/01.HYP.0000231662.77359.de
20. Wright JT Jr A randomized trial of intensive versus standard blood-pressure control N. Engl. J. Med. 2015 373 2103 2116 10.1056/NEJMoa1511939 26551272
Wright, J. T. Jr. et al. A randomized trial of intensive versus standard blood-pressure control. N. Engl. J. Med. 373, 2103–2116 (2015).26551272 10.1056/NEJMoa1511939
21. Ettehad D Blood pressure lowering for prevention of cardiovascular disease and death: A systematic review and meta-analysis Lancet 2016 387 957 967 10.1016/S0140-6736(15)01225-8 26724178
Ettehad, D. et al. Blood pressure lowering for prevention of cardiovascular disease and death: A systematic review and meta-analysis. Lancet 387, 957–967 (2016).26724178 10.1016/S0140-6736(15)01225-8
22. Julius S Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: The VALUE randomised trial Lancet 2004 363 2022 2031 10.1016/S0140-6736(04)16451-9 15207952
Julius, S. et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: The VALUE randomised trial. Lancet 363, 2022–2031 (2004).15207952 10.1016/S0140-6736(04)16451-9
23. Kim JL Long-term clinical outcomes according to the mean observed blood pressure in patients with coronary artery disease after drug-eluting stent implantation J. Hypertens. 2019 37 1898 1905 10.1097/HJH.0000000000002127 31045965
Kim, J. L. et al. Long-term clinical outcomes according to the mean observed blood pressure in patients with coronary artery disease after drug-eluting stent implantation. J. Hypertens. 37, 1898–1905 (2019).31045965 10.1097/HJH.0000000000002127
24. Messerli FH Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann. Intern. Med. 2006 144 884 893 10.7326/0003-4819-144-12-200606200-00005 16785477
Messerli, F. H. et al. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous?. Ann. Intern. Med. 144, 884–893 (2006).16785477 10.7326/0003-4819-144-12-200606200-00005
25. Böhm M Achieved blood pressure and cardiovascular outcomes in high-risk patients: Results from ONTARGET and TRANSCEND trials Lancet 2017 389 2226 2237 10.1016/S0140-6736(17)30754-7 28390695
Böhm, M. et al. Achieved blood pressure and cardiovascular outcomes in high-risk patients: Results from ONTARGET and TRANSCEND trials. Lancet 389, 2226–2237 (2017).28390695 10.1016/S0140-6736(17)30754-7
26. Bangalore S J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial Eur. Heart J. 2010 31 2897 2908 10.1093/eurheartj/ehq328 20846991
Bangalore, S. et al. J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial. Eur. Heart J. 31, 2897–2908 (2010).20846991 10.1093/eurheartj/ehq328
27. McEvoy JW Diastolic blood pressure, subclinical myocardial damage, and cardiac events: Implications for blood pressure control J. Am. Coll. Cardiol. 2016 68 1713 1722 10.1016/j.jacc.2016.07.754 27590090
McEvoy, J. W. et al. Diastolic blood pressure, subclinical myocardial damage, and cardiac events: Implications for blood pressure control. J. Am. Coll. Cardiol. 68, 1713–1722 (2016).27590090 10.1016/j.jacc.2016.07.754
28. Denardo SJ Coronary revascularization strategy and outcomes according to blood pressure (from the International Verapamil SR-Trandolapril Study [INVEST]) Am. J. Cardiol. 2010 106 498 503 10.1016/j.amjcard.2010.03.056 20691307
Denardo, S. J. et al. Coronary revascularization strategy and outcomes according to blood pressure (from the International Verapamil SR-Trandolapril Study [INVEST]). Am. J. Cardiol. 106, 498–503 (2010).20691307 10.1016/j.amjcard.2010.03.056
29. Ndrepepa G Validation of the Bleeding Academic Research Consortium definition of bleeding in patients with coronary artery disease undergoing percutaneous coronary intervention Circulation 2012 125 1424 1431 10.1161/CIRCULATIONAHA.111.060871 22344040
Ndrepepa, G. et al. Validation of the Bleeding Academic Research Consortium definition of bleeding in patients with coronary artery disease undergoing percutaneous coronary intervention. Circulation 125, 1424–1431 (2012).22344040 10.1161/CIRCULATIONAHA.111.060871
30. Urban P Defining high bleeding risk in patients undergoing percutaneous coronary intervention: A consensus document from the Academic Research Consortium for High Bleeding Risk Eur. Heart J. 2019 40 2632 2653 10.1093/eurheartj/ehz372 31116395
Urban, P. et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: A consensus document from the Academic Research Consortium for High Bleeding Risk. Eur. Heart J. 40, 2632–2653 (2019).31116395 10.1093/eurheartj/ehz372
31. Gorog DA De-escalation or abbreviation of dual antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention: A Consensus Statement from an international expert panel on coronary thrombosis Nat. Rev. Cardiol. 2023 20 830 844 10.1038/s41569-023-00901-2 37474795
Gorog, D. A. et al. De-escalation or abbreviation of dual antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention: A Consensus Statement from an international expert panel on coronary thrombosis. Nat. Rev. Cardiol. 20, 830–844 (2023).37474795 10.1038/s41569-023-00901-2
32. D'Ascenzo F Average daily ischemic versus bleeding risk in patients with ACS undergoing PCI: Insights from the BleeMACS and RENAMI registries Am. Heart J. 2020 220 108 115 10.1016/j.ahj.2019.10.001 31809991
D’Ascenzo, F. et al. Average daily ischemic versus bleeding risk in patients with ACS undergoing PCI: Insights from the BleeMACS and RENAMI registries. Am. Heart J. 220, 108–115 (2020).31809991 10.1016/j.ahj.2019.10.001
33. Subherwal S Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: The CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score Circulation 2009 119 1873 1882 10.1161/CIRCULATIONAHA.108.828541 19332461
Subherwal, S. et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: The CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation 119, 1873–1882 (2009).19332461 10.1161/CIRCULATIONAHA.108.828541
34. Böhm M Cardiovascular outcomes, bleeding risk, and achieved blood pressure in patients on long-term anticoagulation with the thrombin antagonist dabigatran or warfarin: Data from the RE-LY trial Eur. Heart J. 2020 41 2848 2859 10.1093/eurheartj/ehaa247 32385506
Böhm, M. et al. Cardiovascular outcomes, bleeding risk, and achieved blood pressure in patients on long-term anticoagulation with the thrombin antagonist dabigatran or warfarin: Data from the RE-LY trial. Eur. Heart J. 41, 2848–2859 (2020).32385506 10.1093/eurheartj/ehaa247
35. Filiberto AC Intraoperative hypotension and complications after vascular surgery: A scoping review Surgery 2021 170 311 317 10.1016/j.surg.2021.03.054 33972092
Filiberto, A. C. et al. Intraoperative hypotension and complications after vascular surgery: A scoping review. Surgery 170, 311–317 (2021).33972092 10.1016/j.surg.2021.03.054
