In this study of Korean subjects who underwent PCI for CAD, it was found that the relationship between BP and all-cause mortality follows a J-shaped relationship in terms of both SBP and DBP. And the identified nadir BP point that was related to the lowest all-cause mortality in this study was 119/74 mmHg, which was lower than that of the value recommended in preexisting guidelines. This study suggests that intensive BP lowering is effective in this patient population, but it is necessary to appropriately control BP especially when considering age, because of the high risk of mortality from excessive BP lowering. As there is a high risk of mortality from low DBPs in elderly patients, it is important to apply a less strict target for diastolic BP reduction in this population.
Interpretation and comparison with other studies
In this study of Korean subjects who underwent PCI for CAD, it was found that the relationship between BP and all-cause mortality follows a J-shaped relationship. Similar results have been indicated in previous studies in CAD patients; however, the identified nadir BP point that was related to the lowest all-cause mortality in this study was 119/74 mmHg, which is lower than the latest known value. In the Treating to New Targets trial, the BP nadir (the nadir BP value found to be associated with the lowest incidence of death due to CAD and non-fatal MI) was 146.3/81.4 mmHg13. The analysis of patients in the PROVE IT-TIMI (PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) trial showed that the BP nadir, which had the lowest incidence of primary outcomes such as all-cause mortality and MI, was 136/85 mmHg14. In the analysis of patients who underwent coronary revascularization among those who participated in INVEST (INternational VErapamil SR-trandolapril STudy), the BP nadir, which had the lowest prevalence of primary outcomes such as all-cause mortality and non-fatal MI, was 145/80 mmHg in the PCI-treated group17. In the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial), the SBP nadir, which had the lowest percentage of primary outcomes such as cardiovascular death, MI, and stroke, was about 130 mmHg12. Overall, the nadir BP proved to have the lowest prevalence of primary outcomes in previous studies tended to be higher than that in our study. On the contrary, in the analysis of patients who participated in INVEST, the BP nadir that had the least occurrence of all-cause death, non-fatal MI, and non-fatal stroke was 119/84 mmHg, similar to the results of this study23.
In particular, as shown in recent studies, intensive BP lowering that targets an SBP of < 120 mmHg may have a positive effect on the long-term survival of CAD patients who had undergone PCI24,25. In addition, this study showed that antihypertensive administration for BP control in patients with a PCI history who had BP below the hypertension criterion could have survival benefits. This is consistent with the results of a previous meta-analysis showing that lowering BP through antihypertensive treatment may be beneficial in patients with a cardiovascular disease history but without hypertension26.
It is particularly noteworthy that when the subjects were divided by age group, there was a difference in the relationship between BP and all-cause mortality in young adults aged < 60 and > 60 years. Younger adults with SBP between 100 and 110 mmHg tended to have the lowest mortality, whereas those aged > 60 years had the lowest mortality when SBP was between 120 and 130 mmHg. This is similar to the results of a previous study in patients with CAD whose SBP values with the lowest all-cause mortality, cardiovascular mortality, MI, and other outcomes increased in the elderly population4,16. It is also consistent with the existing guidelines recommending relatively less strict BP targets for elderly hypertensive patients8,9.
Implications for research and practice
The debate between “the lower the better” hypothesis and the “J-curve phenomenon” hypothesis has long persisted in setting BP control goals11,27. Many studies have shown that mortality and cardiovascular adverse events increase at high and low BP values. Nevertheless, previous meta-analyses and the recent SPRINT study have shown that intensive BP lowering to SBP < 120 mmHg positively affects mortality and other outcomes24,25,28. This supports “the lower the better” hypothesis in BP, which also influenced the guidelines published by the American College of Cardiology and the American Heart Association in 20177. The results of this study showed a high prevalence of all-cause mortality in both the low SBP and DBP groups, suggesting that there is a J-curve relationship between BP and death in CAD patients who had undergone PCI. At the same time, the results of this study also suggest that intensive BP lowering targeting an SBP of < 120 mmHg may have a survival benefit for CAD patients who had undergone PCI. It is important to consider that the actual rate of BP control by antihypertensive medication is only about 70% in Korean patients in 201629. Therefore, physicians in the clinical field should not hesitate to actively control the BP of patients who had undergone PCI.
Although there is a J-curve relationship between blood pressure and all-cause mortality, the CAD patients who underwent PCI can benefit from intensive BP lowering. In this study, we covered only all-cause mortality as outcome. In addition to all-cause mortality, studies are needed to investigate cardiovascular outcomes such as recurrent MI and stroke.
Strengths and limitations of this study
This study has some limitations. First, this study analyzed the results of one-time measurement of BP during the subjects’ health examination. Therefore, this study does not reflect the fluctuation of BP values and, consequently, the measurement of BP may be inaccurate. Second, as the subjects were patients who had undergone a medical examination after undergoing PCI for CAD, there is a risk of selection bias in that patients who were relatively healthy and who were merely interested in health care may have been included. Third, the occurrence of cause-specific mortality or any other related cardiovascular event could have be ignored because only all-cause mortality was calculated as the outcome. Fourth, this study targeted those who underwent PCI within 2 years of receiving a medical checkup. Therefore, there is a limitation in that the interval between the time when PCI was performed and the time when BP was measured among the subjects of this study is not constant, which may have affected the results. Nevertheless, this study examined the incidence of mortality in CAD patients who survived after PCI, as well as obtained specific results and provided important insights into the management of this particular patient population. Moreover, the risk of reverse causality was reduced by excluding patients who died early after PCI and by adjusting for various factors including lifestyle and underlying diseases. This study also has strength in that the average follow-up period was at least 7 years, providing powerful evidence for the long-term management of CAD survivors.
In conclusion, the results of this study in CAD patients who underwent PCI suggests that the mortality was the lowest in BP corresponding to intensive BP lowering in this patient population. Although there is a J-curve relationship between BP and all-cause mortality, the CAD patients who underwent PCI can benefit from intensive BP lowering. This study only covered all-cause mortality as outcome. In addition to all-cause mortality, studies are needed to investigate cardiovascular outcomes such as recurrent MI and stroke.
