Stroke mortality is the second highest in the world, accounting for approximately 9.5% of all deaths, and 5,100,000 of the 167,000 cardiovascular and cerebrovascular patients die of stroke each year. China and *** have the highest stroke mortality rates in the world. The annual number of stroke deaths in China alone is almost as high as the number of stroke deaths in all developed countries. Overall, 2/3 or more of stroke deaths occur in developing countries. The initial incidence of stroke is 141-219 per 100,000; 1/3-1/2 of deaths occur in the year of initial onset, and about 80% of strokes are ischemic strokes. Ischemic strokes include TIA, lacunar infarction and cerebral infarction. Once an individual has had a stroke, the risk factors for recurrent stroke are 8-12% per year, and the risk of infarction is 2-3 times higher.
Indeed, 30 days after stroke, patients saved from stroke are more likely to die from cardiovascular disease than from cerebrovascular events. Therefore, hypertension, a common risk factor for cardiovascular disease, needs to be discussed as a topic.
I. Pathophysiology.
Brain weight is about 2% of body weight, while brain oxygen consumption is 10% of systemic oxygen consumption. The normal value of cerebral blood flow (CBF) is about 50ml-55ml/100g/mL, with 65-75ml/100g/min for gray matter and 35-40ml/100g/min for white matter.
The total output of the heart is 5,000ml/min, and the blood required for normal CBF of the brain tissue is 10% of the cardiac output, of which the flow through the internal carotid artery is 300-400ml/min and the flow through the vertebral artery is 200ml/min.
When cerebral blood flow is progressively reduced due to progressive narrowing and occlusion of cerebral vessels or local blood pressure reduction, once it falls below the perfusion domain, brain function and structural impairment can occur. When rCBF is 20ml/100g/min, the tissue becomes hypoxic and glycogen is anaerobically decomposed; when rCBF is 19ml/100g/min, EEG activity is inhibited; when rCBF is 15ml/100g/min, cortical evoked potentials disappear; when rCBF is 8ml/100g/min, a large amount of potassium ions are released in brain cells, at this time, if perfusion is restored in time, it is possible to save the dying brain. If the perfusion is restored in time, the dying brain cells can still be saved, but if the cerebral blood flow is not restored rapidly, it will lead to irreversible damage to brain tissue.
Morphological observation shows that mitochondrial swelling and astrocyte peduncle edema appear in brain tissue at 3h of ischemia; brain tissue changes are not obvious at 6h, which is still reversible; cell structure destruction appears between 6-12h; local edema appears at more than 2 days; punctate hemorrhage appears in infarct foci at more than 3 days. The thrombus is autolytic and mostly starts to autolyze after 18 hours. Central necrosis appears in ischemic lesions at 1 week; central liquefaction occurs in infarct foci at 3 weeks, which are engulfed and removed; gelatinous scar forms in small lesions at 6 weeks, and stroke capsule forms in large lesions; this period is also called recovery period, which can last from several months to 1 or 2 years.
A decrease in arterial pressure of 1.3 Kpa (10 mmHg) in normal subjects is associated with a 2-7% reduction in CBF.
After local cerebral ischemia, irreversible necrosis of brain cells in the central ischemic area occurs within 5-8 minutes. At this time, there are still a large number of dormant neurons in the peripheral semidark zone. Although these neuronal cells have lost their functions, their damage is reversible, and most of them can be repaired if reperfusion can be obtained within 3-6 hours. Beyond 6 hours, peripheral tissues and collateral circulation still require sufficient blood pressure to maintain perfusion so that the infarct area can be kept to a minimum as possible.
Beyond 6 hours of cerebral tissue ischemia, the peripheral tissues and collateral circulation still require adequate blood pressure to maintain perfusion so that the infarct area can be minimized as much as possible. Between 6 and 24 hours of onset, thrombolysis is not an option at this stage because tissue destruction has reached the cellular level, revascularization causes reperfusion hemorrhage, and thrombus mostly begins to autolyze after 18 hours. In more than 9 international clinical trial studies, the bleeding cases treated with heparin or low-molecular heparin anticoagulation were mainly concentrated in patients within 20 hours.
Aggressive dehydration is advocated for cerebral infarction of moderate or higher volume at 1g/kg per dose, 2-4 times daily depending on the condition, usually for 7 consecutive days, while neuroprotective agents can be applied. Calcium antagonists can release vasospasm, reduce local brain tissue damage, and have the effect of neuroprotection and reducing tissue damage. Cerebral edema is the main conflict during 24-72h of onset, and dehydration should be enhanced. Mannitol and glycerol fructose can be used alternately. If the patient comes to the doctor in this period, it is recommended to temporarily refrain from using strong volume expanders (poppy bases, etc.) to prevent bleeding.
Conditions for reperfusion of the brain.
1. The thrombus does not completely block the blood vessel and may still allow a small amount of blood to perfuse;
2.The pressure in the proximal artery before the thrombus;
3, Adequate blood flow in the proximal artery itself.
Conditions for the opening of collateral circulation.
1.Sufficient pressure in the proximal artery;
2.Sufficient blood flow in the proximal artery;
3. Good collateral vascular conditions.
II. Stroke unit and thrombolysis.
The Stroke Unit is the most effective treatment for acute ischemic stroke based on evidence-based analysis, firstly the Stroke Unit and secondly thrombolysis. Stroke Unit staff includes clinicians, specialized nurses, physical therapists, occupational therapists, speech and language trainers, and social workers.
The time window for thrombolytic therapy in the United States and Europe is within 3 hours and the drug is r-tPA, 0.9 mg/kg; while in China the time window is within 6 hours; the drug is UK, 1-1.5 million units or r-tPA, 0.9 mg/kg.
III. Blood pressure regulation in acute ischemic stroke.
When acute stroke occurs, most individuals have a reflexive increase in blood pressure, and the question of what level of blood pressure is appropriate to maintain at this time is exactly what we propose to discuss. It is now believed that the blood pressure in the acute phase of ischemic stroke is not advocated to be rapidly and aggressively lowered to the usual ideal level, but rather to be maintained at a relatively high level for a week.
(i) Presentation of a Spanish study.
A recent Spanish clinical study analyzed blood pressure fluctuations, CSS, CT volumes and mortality in 250 hemispheric ischemic stroke patients within 24 hours after onset and compared them with the results three months later and found that patients in the lowest and highest systolic and lowest and highest diastolic groups on the day of onset had the greatest loss of neurological function and the largest infarct volumes shown on CT three months after the disease. The study also found that patients in the lowest systolic and lowest diastolic groups had the most severe loss of neurological function and the highest mortality rate in the early phase of the disease (7-8 h).
The study noted that those who lowered their blood pressure rapidly within 24 hours of hospitalization, if they lowered their systolic blood pressure by more than 30 mmHg and their diastolic blood pressure by more than 20 mmHg, also had severe neurological loss early on and a large infarct size, and a high CSS score at 3 months. This study also suggests that too high or too low blood pressure, as well as rapid lowering of blood pressure, can exacerbate ischemic injury in the hemisphere.
(ii) US study.
The American scholar Caplan in Caplan’s Stroke 2000 edition states that in acute stroke, rapid and violent lowering of blood pressure does not reverse acute stroke because of the effect of years of hypertension on the vessel wall. In fact, aggressive lowering of blood pressure may reduce cerebral perfusion, and low perfusion will cause increased neurological damage. In some individuals with flow-dependent stroke, the need for blood pressure is often more urgent, and adequate perfusion must be maintained within a week of stroke onset until collateral circulation is established.
(iii) ACEI and stroke blood pressure regulation.
A professor from Oxford University, UK, reported the results of a study related to HOPE (The Heart Outcome Prevention Evaluation). A controlled study of cardiovascular patients on oral Ramipril ramipril 10 mg/day or placebo with 4.5 years of follow-up. The results showed a 22% reduction in cardiovascular death, non-fatal stroke and myocardial infarction rates overall, and a 32% reduction in stroke incidence. This study was the result of taking a single ACE inhibitor, unlike the study with a combination of blood pressure lowering, lipid lowering and aspirin. Subgroups were based on sex, age, diabetes group and other concomitant disease groups.
ACE inhibitors had little effect on lowering blood pressure, with a mean decrease in SBP of 3.3 mmHg and a decrease in DBP of 1.4 mmHg.
Why is there no effect on blood pressure but a desirable effect on the prevention of vascular disease? The possible explanation is that ACE inhibitors counteract the damaging effects of angiotensin II on the vessel wall, heart, atherosclerotic plaque and endothelium.
In the HOPE study, unlike previous community-based population surveys and clinical large sample studies, normotensive cardiac patients >= 55 years of age were administered the drug and followed for 4.5 years. sBP was well controlled and had a good preventive effect, p<=0.009. In the subgroup, the non-diabetic group was excluded for patients with uncontrolled blood pressure, and this group was excluded for patients with hypertensive disease. The blood pressure level of those enrolled was required to be below 138/80 mmHg. The low blood pressure in this group was mostly due to coronary artery disease and beta-blocker administration. Regardless of whether the blood pressure was high or low, the subgroup results were, in general, significant.
Therefore, this study suggests that ACEI is partly responsible for lowering blood pressure, but also has other unexplored functions. Angiotensin receptor antagonists have selective blockade of AT-1 receptors and inhibition of inflammatory responses and have desirable hypotensive effects.
(iv) Age and blood pressure.
Not all stroke patients in all age groups should have their blood pressure lowered. There are findings that stroke patients under 55 years of age are prone to elevated blood pressure at the onset and require blood pressure lowering drugs; this group of hypertensive patients should be treated with anti-hypertensive drugs for years and have their blood pressure reduced to 120-139/80 mmHg or less. The results of the study suggest that patients aged 55-64 years with hypertension should also be treated with antihypertensive drugs for years, with blood pressure falling below 140-160/89 mmHg depending on individual conditions. 65-81 year olds with blood pressure below 160/90 mmHg are best treated without hypotensive therapy, as 70% of patients in this age group have organ disease and low blood pressure is a risk factor for stroke in them.
(v) Thrombolytic therapy and blood pressure.
A large sample of rt-PA thrombolysis for acute ischemic stroke within 3 hours in the US NINDS requires that blood pressure above 185/110 mmHg be considered for antihypertensive treatment. The requirement of UK thrombolysis for acute ischemic stroke within 6 hours by Prof. Chen Qingtang in China’s Ninth Five-Year Plan, blood pressure is considered for hypotensive treatment when it is 180/100mmHg. The standardized treatment of cerebrovascular disease by Prof. Huang Yining in our 15th research project, the requirement of acute ischemic stroke within 6 hours of UK thrombolysis treatment is to consider antihypertensive treatment when the blood pressure is 185/100mmHg.
IV. Conclusion.
Taken together, we conclude that for blood pressure regulation, it should be managed according to age, stroke risk factors and stroke type. It is also inappropriate to provide aggressive antihypertensive therapy to all patients with acute ischemic stroke. Patients with previous hypertension should maintain blood pressure levels of 160-180/100-105 mmHg; in patients without previous hypertension, blood pressure should be maintained at 160-180/90-100 mmHg; when blood pressure is higher than 200 /105 mmHg, cautious antihypertensive therapy may be considered.