Hypertension is a serious threat to human health, and its large number of patients and difficulty in controlling the disease have attracted widespread attention from the medical community. At the same time, as a high-risk factor for cardiovascular diseases, patients with hypertension are often clinically combined with one or more chronic diseases such as coronary heart disease, diabetes, stroke, etc. The mortality rate caused by cardiovascular diseases has risen to the first place of all diseases mortality. Therefore, aggressive and effective blood pressure control is essential to improve the quality of life and extend the average life expectancy of the affected population.
While the benefits of aggressive BP lowering are clear, what is a reasonable target value has been the subject of debate in the medical community, and both the JNC7 and the 2007 European Guidelines for the Management of Hypertension recommend lowering BP to below 140/90 mmHg in patients without comorbidities and to below 130/80 mmHg in patients with comorbid diabetes, cardiovascular disease, or chronic kidney disease. mmHg or less. The traditional “thelower,thebetter”; however, in recent years a large number of clinical studies have questioned this view, and new clinical trials have found that when blood pressure falls below a certain threshold, the incidence of cardiovascular events and overall mortality increases rather than decreases. This is known as the J-shaped curve phenomenon, or J-curve for short, and this critical point of blood pressure reduction is also called the J-point.
In view of the clinical complexity of hypertensive patients, this paper will review the target values of blood pressure reduction for patients with ischemic heart disease, diabetic patients, patients with cerebrovascular disease, patients with chronic kidney disease, and elderly patients with hypertension, respectively.
1.Patients with ischemic heart disease
Unlike other important organs, blood perfusion in the coronary arteries occurs mainly in the diastolic phase of the heart, which means that once blood pressure is lowered, coronary perfusion will be more sensitive to changes in diastolic pressure. This has been confirmed by clinical studies.
However, recent studies have suggested that the same J-shaped curve exists for systolic blood pressure and ischemic heart disease. In addition to the post hoc analysis of Invest by Messerli et al. in 2006, the 2009 ONTARGET study followed 25,588 hypertensive patients, aged 55 years or older, with comorbid coronary artery disease, cerebrovascular disease or diabetes mellitus with end-organ damage on antihypertensive therapy and found that when systolic blood pressure was reduced below 130 mmHg, the benefit came mainly from a stroke The risk of myocardial infarction and cardiovascular death did not decrease and even increased. In light of this finding, Sleight proposed that “future studies should aim to evaluate the impact of systolic blood pressure reduction in high-risk patients with systolic blood pressures in the 130-150 mmHg range.”
2. Diabetic patients
Atherosclerosis is more prevalent in the diabetic population than in the non-diabetic population and mainly affects the aorta, coronary arteries and cerebral arteries, causing coronary heart disease, ischemic or hemorrhagic stroke, and is now considered an independent risk factor for cardiovascular mortality.
Although numerous clinical studies in recent years have revealed a J-shaped curve between low blood pressure, especially diastolic blood pressure, and the incidence of cardiovascular events, some scholars still question this phenomenon. The challenge mainly comes from the following aspects: some of the clinical studies did not observe the J-shaped curve; for the clinical trials where the J-shaped curve phenomenon was observed, most of them used post hoc analysis, which undoubtedly affects the credibility of the analysis results to some extent; for the post hoc analysis of Invest conducted by Messerli et al. in 2006, some scholars concluded that some of the patients enrolled had low baseline diastolic blood pressure and therefore, with or without antihypertensive treatment, there was consistently a higher incidence of cardiovascular events in these populations themselves. This also confounded the results of the analysis.
Thus, there is still much debate about the J-shaped curve in antihypertensive therapy in patients with diabetes and high cardiovascular risk, which requires in-depth study of this issue in large, prospective clinical trials with different levels of blood pressure lowering.
3.Patients with cerebrovascular disease
Like coronary arteries, the brain has a strong vascular self-regulation ability, which is influenced by various factors such as sympathetic nervous system, renin-angiotensin-aldosterone system, partial pressure of arterial blood oxygen and partial pressure of carbon dioxide. The difference is that blood perfusion in the cerebral vasculature depends mainly on systolic pressure and is less influenced by diastolic pressure. This physiological mechanism explains why Messerli et al. and Sleight et al. did not observe a J-shaped curve between diastolic and systolic blood pressure and stroke. Furthermore, the ONTARGET study by Sleight et al, while alerting people to excessive blood pressure lowering in patients at high cardiovascular risk, also revealed that patients with systolic blood pressure below 130 mmHg could benefit from a reduction in stroke. Earlier studies have also found that patients with prior cerebrovascular disease can benefit from intensive blood pressure lowering.
Yusuf et al. randomized 20,332 patients with a recent history of ischemic stroke to receive telmisartan (80 mg/d) and a placebo group, with recurrent stroke as the primary endpoint and major cardiovascular events and new-onset diabetes as secondary endpoints. At a mean follow-up of 2.5 years, the results showed that antihypertensive treatment with temisartan in patients with a recent history of ischemic stroke did not significantly reduce the risk of recurrent stroke, major cardiovascular wind events, and new-onset diabetes. Although this finding is controversial, it suggests that more evidence-based medical evidence is needed to determine whether “thelower,thebetter” is appropriate for antihypertensive therapy in patients with cerebrovascular disease.
4.Patients with chronic kidney disease
Chronic kidney disease and hypertension are mutually beneficial. Chronic kidney disease, with its increased sympathetic excitability and water and sodium retention, is involved in the formation and development of hypertension, while hypertension can lead to further deterioration of kidney function and accelerate the process of end-stage renal disease. Therefore, treatment of hypertension has become one of the most important aspects of the various management modalities for chronic kidney disease.
Most hypertension guidelines recommend that blood pressure should be lowered to below 130/80 mmHg in patients with chronic kidney disease. The MDRD study, the AASK study, and the REIN-2 study, which enrolled patients with chronic kidney disease or non-diabetic kidney disease, all used end-stage renal disease as the primary observation and showed that intensive blood pressure lowering did not delay the progression of end-stage renal disease to the additional benefit of these patients.
For patients with nephropathy with 24-h urine protein quantification greater than 1 g, lowering blood pressure to below 125/75 mmHg has been recommended in the past. However, this conclusion, which was largely based on a post hoc analysis of the MDRD study, was unconvincing and JNC7 therefore removed this detail. This is despite the fact that one meta-analysis of patients with kidney disease treated with dialysis claimed that a 4.5/2.3 mmHg reduction in systolic/diastolic blood pressure resulted in a 29% reduction in cardiovascular events, a 20% reduction in all-cause mortality, and a 29% reduction in cardiovascular disease mortality. However, no definitive answer is given for the exact target value of blood pressure reduction. Moreover, there is a lack of such prospective trials, making the blood pressure lowering targets for patients with proteinuria inconclusive.
In fact, no studies have shown that blood pressure targets below 130/80 mmHg in patients with chronic kidney disease save lives, protect the kidneys, or reduce cardiovascular events. In light of this, Agarwal believes that a reasonable blood pressure target for most patients with chronic kidney disease should be less than 140/90 mmHg.
5. Hypertension in the elderly
As mentioned earlier, low diastolic blood pressure can affect coronary perfusion, leading to an increased risk of ischemic heart disease, while high systolic blood pressure and cardiovascular events have also been shown to have a J-shaped curve. However, high systolic blood pressure and cardiovascular events have also been shown to have a J-shaped curve. Even so, hypertension treatment guidelines still recommend aggressive blood pressure control, and Wang et al. found that antihypertensive therapy in older adults with diastolic blood pressure less than 70 mmHg still reduced the incidence of cardiovascular events, stroke, and myocardial infarction, and that the benefit increased with age. It is suggested that the cardiovascular benefit is mainly through lowering systolic blood pressure.
The HYVET study by Beckett et al. enrolled hypertensive patients aged 80 years and older with a target BP reduction of 150/80 mmHg and showed that even hypertensive patients aged 80 years and older could benefit from BP reduction. There is also evidence that the percentage of hypertensive patients over 65 years of age who benefit is not lower than that of relatively young patients. Therefore, aggressive antihypertensive treatment can also lead to cardiovascular benefits in the elderly.
The 2005 Chinese hypertension guidelines currently used in China suggest that systolic blood pressure in the elderly should be lowered to below 150 mmHg, with further reductions if tolerated, and the 2009 update of the European hypertension guidelines advocates that elderly patients with hypertension should also be treated with aggressive antihypertensive therapy, but suggests that there are no clinical studies to support the benefit of lowering systolic blood pressure to below 140 mmHg.
Oqihara et al. enrolled 1500 hypertensive patients aged 60 years and older who had tolerated candesartan monotherapy for at least 8 weeks and maintained their blood pressure below 140/90 mmHg during 3 years of follow-up and found that patients with higher blood pressure tended to have a higher incidence of cardiovascular events. And the incidence of cardiovascular events was significantly higher in patients with post-treatment systolic blood pressure below 120 mmHg compared with patients aged 75 years and older with post-treatment systolic blood pressure between 120 and 139 mmHg. Alternatively, aggressive blood pressure lowering in the elderly is not advocated along with excessive blood pressure lowering in them.
6. Conclusion
In conclusion, the target values of blood pressure lowering vary in different populations, and many areas are currently inconclusive. In addition, the clinical condition of hypertensive patients is often complex and variable, and for patients with a combination of different chronic diseases, how to weigh the advantages and disadvantages of lowering blood pressure will be the focus of future research. It is also important to recognize that despite the availability of effective drug combinations, the percentage of patients whose blood pressure meets the guideline target is very low, so it is important to take proactive and effective measures to develop individualized treatment plans for different hypertensive populations while emphasizing the importance of not over-lowering blood pressure.