The impact of antihypertensive drugs therapy on the quality of life of post-cerebral stroke patients
 
Fangfang Zhu
Xuzhou Medical College Hospital Emergency Center, Jiangsu Province, Xuzhou, 212003
 
Abstract: As the population around the world is rapidly aging, cerebral stroke has become one of the major diseases that threatened human health. Hypertension could potentially act as both the cause and result of cerebral stroke. The closely linked relationship between these two conditions means that the monitoring of blood pressure might affect the occurrence and recurrence of cerebral stroke, even potentially affecting the future prognosis. While there are a wide variety of antihypertensive drugs available, different types of drugs have a different effect on the  quality of patients’ lives. Therefore, more in depth understanding of the drugs’ characteristics will be beneficial for the treatment of individual patients, which in turn leads to an improvement of their quality of life.  
 
Keywords: hypertension; cerebral stroke; antihypertensive drugs; quality of life
  
Citation: Zhu FF. The impact of antihypertensive drugs therapy on the quality of life of post-cerebral stroke patients. J Gen Neuro; 1(1):
^*Correspondence to: Fangfang Zhu, Xuzhou Medical College Hospital Emergency Center, Jiangsu Province, Xuzhou, 212003, email address.[H1] 
Received:                          Accepted:                     Online Published:
 
Introduction
Hypertension is one of the major risk factors affecting the onset and development of cerebral stroke^[1]. The regulation of blood pressure level is the primary method of intervention that could lower the incidence and mortality rate caused by cerebral stroke^[2]. Hypertension is also a risk factor leading to the recurrence of cerebral stroke. Hence, antihypertensive therapy is an effective measure for the secondary prevention of cerebral stroke^[3]. As such, effective treatment and control of high blood pressure is the key in cerebral stroke prevention.
 
 
The epidemiological characteristics of hypertension and cerebral stroke
A Meta-analysis on the effect of lowering blood pressure in elderly patients with moderate hypertension has been evaluated and the results suggested that lowering blood pressure level could reduce the incidence rate of cerebral stroke in 42% of the patients. Results from extensive clinical research data for acute ischemic stroke patients with spontaneous intracerebral hemorrhage showed significant correlation between patients with hypertension and the mortality and disability rates, and  its subsequent deterioration. A moderate drop in blood pressure of the patients with moderate hypertension could effectively improve their future prognosis.
A systematic review by Rashid et al. also led to the same conclusion^[4]. The authors supported the administration of antihypertensive therapy to post-cerebral stroke patients, in order to significantly reduce the rate of recurrent stroke and other cerebrovascular conditions. Huang et al. found that patients with hypertension have a strong correlation between stroke and the fasting glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), the age and HDL-C^[5]. Family history of hypertension was independently associated with stroke. Pang et al. carried out a comprehensive assessment of various risk factors and potential interventions measures for the primary prevention of stroke^[6]. Among the various strategies available, regulation of blood pressure level is the key factor for stroke prevention. The hypertension and stroke epidemiological data showed that for every 5 mmHg drop in diastolic blood pressure, the risk of stroke for hypertensive patients could be reduced by one third.    
A foreign study found that active antihypertensive measures could greatly reduce the incidence of stroke^[7]. Clinical study showed that for patients receiving antihypertensive treatment, about 27% of ischemic stroke and 57% of hemorrhagic stroke were caused by improper regulation of blood pressure level. Furthermore, for the two groups of patients who underwent antihypertensive therapy, the group of patients that terminated their treatment after a certain period experienced a greater risk of stroke compared to those who did not terminate their treatment. Currently there is no direct evidence showing that the termination of treatment leads to increased incidence of stroke. While constant antihypertensive therapy, blood pressure monitoring and increased patient compliance through education may not be sufficient in order to reduce blood pressure to the ideal level, it might still be effective in reducing stroke incidence to a significant extent^[8].   
An international stroke study claims that extremely high or low blood pressure levels are the risk factors contributing to poor prognosis^[9]. In this study, it was found that post-stroke sustained hypertension is a risk factor affecting the possibility of recurrence within 14 days. Hence, the high blood pressure is a risk factor directly affecting the incidence of ischemic stroke or hemorrhagic stroke. Several studies show that the increase in monitoring and controlling of hypertension, TIA and lipid levels are effective measures for preventing stroke recurrence^[10].
According to a report by Wang et al., clinical evidence showed that for secondary prevention of stroke, in comparison to the control group receiving placebo, the group of patients receiving antihypertension therapy experienced a lower rate of incidence in stroke, coronary heart disease and mortality by 28%, 15% and 11%, respectively^[11]. In addition, antihypertensive therapy not only led to a decrease in stroke and coronary heart disease incidence for patients with hypertension, it could also lower the risk of stroke incidence for patients without hypertension. Hence, effective regulation of blood pressure level is an important measure for the secondary prevention of stroke. The proven controllable risk factors of stroke include hypertension, diabetes, atrial fibrillation, asymptomatic carotid stenosis, smoking, improper diet, dyslipidemia and sedentary lifestyle. Hypertension is the most common among these risk factors. As such, regulation of blood pressure level is beneficial to the prevention of stroke onset and recurrence^[12]. For elderly patients, there is an even closer relationship between systolic hypertension and stroke^[13].       
 
 
Stroke and blood pressure regulation
The blood supply to brain tissues primarily depends on cerebral perfusion pressure, and cerebral perfusion pressure is closely linked to the mean arterial pressure. Under normal circumstances, due to the presence of cerebral autoregulation mechanism, cerebral blood flow is relatively stable. However, the cerebral autoregulation mechanism only functions within a specific range of mean arterial pressure (50 – 160 mmHg). If the mean arterial pressure is out of range, it would result in brain edema and cerebral ischemia. When the cerebral autoregulation mechanism of stroke patients becomes malfunction, brain blood supply is more dependent on the mean arterial pressure. When the mean arterial pressure is too high, it would lead to brain edema and intracranial hemorrhage. On the other hand, mean arterial pressure that is too low could cause cerebral ischemia.
 
Blood pressure regulation for acute hemorrhagic stroke
For patients experiencing acute phase hemorrhagic stroke, high blood pressure might be due to both the cause of stroke and also the results of stroke. Currently, the appropriate blood regulation measures for acute phase hemorrhagic stroke are still under debate. Various versions of hemorrhagic stroke guidelines have provided recommendations on blood pressure regulation. The latest guidelines of the American Heart Association did not offer a recommendation on the specific blood pressure level associated with cerebral hemorrhage and acute cerebral hemorrhage. However, it suggested that antihypertensive measures should be taken when systolic blood pressure is above 200 mmHg or when mean arterial pressure exceeds 150 mmHg^[14].  
The American Stroke Association (ASA) recommends the application of antihypertensive measures according to the specific conditions of the patients. These include the baseline blood pressure of the patients, possible cause of the hemorrhagic stroke, age and the level of intracranial pressure. If the hemorrhagic stroke is caused by cerebral vascular malformations (aneurysms, arteriovenous malformations), there will be an increased risk of continued bleeding and re-bleeding. Hence, active antihypertensive measures are needed under these conditions^[14].   
The Australian guideline recommends that the mean arterial pressure should be maintained at 130 mmHg or below. The European Stroke Association pointed out that patients with a history of hypertension or symptoms of chronic hypertension could sustain a higher level of mean arterial pressure. Hence, their mean arterial pressure should be maintained at about 120 mmHg, but not lower than 84 mmHg. The extent of decrease of mean arterial pressure should be below 20%, in order to prevent brain hypoperfusion.   
An INTERACT study selected 404 cases of hypertensive patients suffering from intracranial hemorrhage and divided them into two groups. These groups are active antihypertensive group (140 mmHg target SBP) and blood pressure regulation according to guideline group (180 mmHg target SBP). Results showed that while a decrease of blood pressure within 72 h of intracranial hemorrhage onset prevented further spreading of hematoma, the edema condition around the hematoma was not significantly affected^[15].
In theory, lowering blood pressure during acute cerebral hemorrhage could slow down the expansion of hematoma and improve future prognosis. However, the relationship between lowering blood pressure and the condition of prognosis is still under debate. Previous studies showed that a constant increase of blood pressure during cerebral hemorrhage leads to poor prognosis^[16,17]. On the other hand, low blood pressure might lead to a decrease of blood flow to brain tissues surrounding the hematoma, causing ischemic injury of these tissues. However, if the cerebral autoregulation mechanism around the hematoma is undamaged, there will be better tolerance towards lower blood pressure. In general, it is safer to have lower blood pressure during cerebral hemorrhage. However, due to concern on low blood pressure induced ischemic injury of surrounded brain tissues, active antihypertensive measures during cerebral hemorrhage is being restricted^[18].       
A study on intensive blood pressure reduction in acute cerebral hemorrhage (ATACH) found that hematoma enlargement usually take place within 24 h of the onset of cerebral hemorrhage symptoms. A comparison between patients underwent intensive antihypertensive treatment and normal antihypertensive treatments showed that the former experienced a significantly decrease of hematoma volume^[19]. After a review of recent data, Wityk concluded that it is safe to carry out low or medium dosage of ICH antihypertensive treatment during acute cerebral hemorrhage. Liu et al. reported 60 cases of elderly patients with hypertensive cerebral hemorrhage who have been administered with antihypertensive drugs when their blood pressure reached or exceeded 170/110 mmHg, and resulted in lowering their blood pressure to the range of 150–160 mmHg / 90–100 mmHg^[20]. The subsequent examination of their CT scan after three days showed that the hematoma for 57 of the patients was not enlarged. The authors concluded that the extent of blood pressure regulation for cerebral hemorrhage patients should depend on pre-hemorrhage blood pressure, intracranial pressure, age, cause of hemorrhage and hemorrhage location. In addition, the lowering of blood pressure should be moderate, in order to prevent lowered cerebral perfusion pressure, which could further aggravate the brain injury. However, ICH-based randomized controlled study for blood pressure regulation during acute cerebral hemorrhage is still limited, in which, the beneficial effect of antihypertensive treatment on future prognosis is yet to be confirmed. Furthermore, the impact of blood pressure level on the patients with cerebral hemorrhage and high intracranial pressure is yet to be evaluated^[21].
                   
Blood pressure regulation for acute ischemic stroke
Clinical studies on the effect of blood pressure regulation during ischemic stroke are still limited. During an ischemic stroke, the cerebrovascular autoregulation of the ischemic penumbra is impaired. The transition from the ischemic penumbra condition to cerebral infarction takes place within 24 h of the ischemic stroke onset. Within 48 h of the cerebral infarction, cerebral blood flow and perfusion is dependent on the level of the body's blood pressure. The elevation of arterial pressure during this period can improve blood flow in the ischemic penumbra perfusion, reduce brain injury and protect brain tissue. On the other hand, low blood pressure can aggravate ischemic penumbra hypoperfusion^[22]. Constant increase of blood pressure during ischemic stroke can intensify brain edema, and increase the risk of stroke recurrence.       
The 2007 American Heart Association and American Stroke Association early control guidelines pointed out that for most patients with acute ischemic stroke, lowering blood pressure during ischemic stroke is not absolutely necessary. A cautious approach should be taken. For patients without thrombolysis indications, when the blood pressure level of SBP >220 mmHg or DBP >120 mmHg is reached, antihypertensive measures should be taken within the first 24 h of cerebral infarction, aiming to reduce blood pressure by 15% (SBP or DBP). For patients with thrombolysis indications, SBP and DBP should be kept below 185 mmHg and 110 mmHg, respectively. After the application of rt-PA, both SBP and DBP should be kept below 180 mmHg and 105 mmHg, respectively^[23].
 The China guideline  recommends that early stage of cerebral infarction treatment should depend on the extent of hypertension level, the overall condition and baseline blood pressure of the patient^[24]. Should the ongoing antihypertensive therapy that the patients have been taking before onset of stroke be terminated when they are stricken with stroke? This question is addressed by the COSSACS multi-center prospective study carried out in the UK. Those stroke patients who were within 48 h of stroke onset and were taking antihypertensive drugs prior to the stroke were selected for this study. They were randomly divided into two groups, whereby 379 patients continued antihypertensive therapy after stroke, and the other 384 patients did not do so. The data analysis on the two-week and 6 months of cardiovascular disease of incidence of death found that the two groups were not statistically different in terms of mortality rate. While the group that continued antihypertensive treatment maintained a relatively lower level of blood pressure, this did not lead to an increase of adverse events^[25].
While the AHA/ASA guidelines recommended a conservative approach in lowering blood pressure level, clinicians generally tend to take active antihypertensive measures towards AIS[H2]  patients. In a review conducted by Underwood et al. in 50 AIS patients with moderate and high hypertension, it was found that while only 22% (N = 11) of the patients meet the AHA/ASA standard guidelines for antihypertensive therapy, 98% of the patients were administered with antihypertensive measures. While patients with relative hypotension (at least once SBP <120 mmHg or MAP <85 mmHg) were common, there were only three cases of patients with absolute hypotension (at least once SBP <90 mmHg or MAP <60 mmHg). It was found out that 11 patients that meet the standard measures for antihypertensive had low blood level beyond the guideline requirement. Hence, the authors believe that early and intensive antihypertensive measures as well as relative and absolute hypotension did not cause the deterioration of neurological functions and prognosis. They suggested the launching of a large scale prospective randomized study to evaluate the effect of reduced drug administration during AIS^[26].      
Several clinical studies found that antihypertensive therapy is beneficial to cerebral infarction patients^[27,28]. Antihypertensive therapy could alleviate brain edema, lower the risk of post-infarction hemorrahage, prevent further damage of cerebral blood vessels and reduce the likelihood of early stage stroke recurrence. Nie et al. studied on whether antihypertensive measures should be taken after stroke and when it should be taken^[29]. The 198 patients were divided into groups and were observed for neurological impairment, cardiovascular events and mortality rate. Results showed that antihypertensive therapy could reduce the incidence rate of cardiovascular events and mortality. The patients who received antihypertensive therapy after three days had significantly improved recovery of neurological functions. A study by Pan et al. showed that excessive measures to reduce blood pressure to its normal range during AIS could lead to increased neurological damage and poor prognosis^[30]. The pros and cons of whether antihypertensive measures can be applied or not should be considered carefully and blood pressure level should be regulated within reasonable range. A study conducted by Luo et al. showed that it is beneficial to lower SBP level to 150–160 mmHg within 24 h of AIS onset (if SBP >170 mmHg)^[31].     
 
Secondary prevention of cerebral stroke
Antihypertensive therapy is an important aspect in the prevention of stroke recurrence. During the recovery period, stroke patients are in recovery phase and their condition is stabilizing. Apart from improving cerebral circulation, promote cell metabolism and strengthening the paralyzed limbs functions by rehabilitation, antihypertensive therapy is also the key to prevent stroke recurrence. Stroke patients with hypertension are considered as high risk group. Hence they actively seek treatment. This is also recommended by hypertension guidelines from various countries.
The AHA / ASA 2011 guideline for AIS / transient ischemic attack (TIA) secondary prevention points out antihypertensive therapy as the primary measure to control the risk of stroke prevention. The guidelines emphasized that antihypertensive therapy should be tailored to the conditions of individual patients and only applied to suitable AIS/TIA patients. The aim of this concept is to prevent the risk to patients due to improper antihypertensive measures^[32]. The year 2006 stroke secondary prevention guideline suggested that stroke patients at the stabilizing phase should have blood pressure level of SBP <130 mmHg and DBP <85 mmHg. However, few studies claimed that this standard is too restricting, which could lead to nocturnal hypotension and increased rate of stroke recurrence^[33]. According to a comprehensive analysis of 4 clinical studies carried out in this country, the risk of stroke was reduced by 36% for every drop of SBP 9 mmHg and/or DBP 4 mmHg^[34]. Faced with a wide variety of antihypertensive drugs available, the suitability of these drugs for secondary stroke prevention is of primary concern.          
As pointed by the AHA / ASA 2010 guideline for stroke secondary prevention, the most suitable antihypertensive drug for secondary prevention of stroke is still unclear^[35]. Large scale clinical studies showed that diuretics and ARB types of antihypertensive drugs have positive effects on secondary stroke prevention. The combined usage of ACEI and diuretics also showed good results. A recent release of a multi-center, randomized, double-blind, placebo-controlled study have shown that for stroke and TIA patients, the administration of 2.5 mg/time, one time/day of Indapamide for two years led to an average blood pressure drop of 6.8/3.3 mmHg. In comparison to the control group, the group of patients who received Indapamide treatment experienced a significantly lower rate of stroke recurrence and cardiovascular events^[36].          
In 2007, a meta-analysis of 26 prospective randomized clinical studies on primary and secondary prevention of stroke showed drugs that elevateⅡ2 angiotensin receptor (AT2R) level, such as thiazide diuretics, angiotensin receptor blockers, and dihydropyridine calcium antagonists not only play the role of reducing blood pressure level, but also have a protective effect in term of lowering stroke incidence. On the other hand, the drugs that reduce AT2R level, such as ACEI, β-blockers, non-dihydropyridine calcium antagonists may weaken the impact of antihypertensive drugs on stroke prevention^[37]. Studies have shown that for the patients with orthostatic blood pressure, it is more important to control their blood pressure fluctuations variability rather than reducing the average blood pressure^[38]. In addition, dihydropyridine calcium antagonist amlodipine is uniquely effective in reducing blood pressure variability and can significantly reduce the incidence of cerebrovascular events^[39].
 
Quality of life and antihypertensive drugs
With the change of disease spectrum and the increase of people's health needs and expectations, the medical model is transitioning from the biomedical model to a bio-psycho-social medical model, thereby the concept of quality of life emerged. Hypertension is a chronic disease that poses serious threat to human health. It has high incidence rate, along with a series of complications. Especially for stroke patients with hypertension, there is a serious impact on quality of life. Currently there are many drugs available for doctors to choose from. While the antihypertensive effects of the drugs are not significantly different from one another, there is a huge difference in terms of adverse drug reactions on the body and the impact on patient QOL[H3] .
 
The concept of QOL and its measurement guideline
According to World Health Organization (WHO), the quality of life is defined as: quality of life of individuals is the impression of their status and conditions within a certain cultural background and value concepts^[40]. It is related to personal goals, expectations and matters of interest for each individual. It is a wide-ranging concept, encompassing the body's health, mental state, independent living, social relationships, personal beliefs and the significant environmental characteristics related to the content of aggregate. Currently, the more widely accepted QOL should include physical, social, spiritual and emotional function, sense of health and life, symptoms and side effects, and so on. At present, the specialized international standard for the measurement of quality of life of hypertension patients is still lacking. A few numbers of the available measurement guidelines for estimating the quality of life for hypertension patients include the World Health Organization's WHOQOL-100 scale (1995) (the well – being questionnaire), the SF–36 scale (the Medical Outcomes 36 Item Short–Form Heath Survey), the NHP scale (Nottingham Health Profile), the Psychological General Wellbeing Index (PGWI), Comprehensive assessment of quality of life questionnaire –74 (GQOLI–74), evaluation of community groups function (COOP / WONCA) and so on.
 
The impact of various types of antihypertensive drugs on quality of life
The quality of life of hypertension patient may be affected by symptoms, blood pressure level, side effects of antihypertensive drugs, the labeling effect, psychological factors, income level, educational status, chronic diseases, age, gender, family history, obesity, etc. This report focuses on the impact of hypertensive drugs on the quality of life of the hypertension patients.  
Current data analysis found that antihypertensive therapy could have a variety of impacts to the quality of life. The first opinion claims that the antihypertensive therapy has a positive effect on quality of life, which may be attributed to the drug or the placebo effect^[41]. Another opposing opinion claims that antihypertensive therapy does not improve the quality of life of patients. Further studies suggest that this might be related to drug induced side effects^[42]. Certain drugs have side effects on the psychological/mental aspect, such as causing depression of patients. The impact of drugs on quality of life depends on many factors, including drug type, usage, dosage, and so on. Currently, there are related research reports on several antihypertensive therapy drugs such as: calcium channel blockers, β-blockers, converting enzyme inhibitors and AnglI antagonists, and diuretics. However, the reported results are not consistent. A classified narrative effect of drugs on quality of life is discussed as follows. 
 
Calcium antagonists (including dihydropyridine and non-dihydropyridine)
Calcium antagonists’ functions are mainly through the inhibition of smooth muscle L-type calcium channel, thereby reducing the concentration of intracellular calcium, causing smooth muscle relaxation, vasodilatation, and thus play a role in lowering blood pressure. It is suitable especially for patients with arrhythmia, angina, peripheral vascular disease and elderly systolic hypertension. However, patients with conduction blockage should be prohibited from using this drug. The main adverse reactions include headache, peripheral edema, facial flushing, constipation, increased sympathetic activity and so on. Short-acting calcium antagonists (such as nifedipine) can improve the quality of life of patients with hypertension (including health status, body symptoms, anxiety, depression, psychiatric symptoms and cognitive function, etc.)^[43].
 Grimm et al. studied the impact of five types of drugs (including long-acting calcium channel blocker amlodipine) on the quality of life^[44]. They investigated 7 aspects and 35 indicators of hypertension patients (overall health, energy, mental health, overall function, body satisfaction, social functioning and contacts, etc.). The improvement of quality of life is significantly correlated to increased exercise and blood pressure regulation. Study conducted by Dahlof et al. and Grimm et al. also confirmed that amlodipine is well-tolerated by patients^[45,46]. In addition, diltiazem^[47], verapamil^[48] can also improve the quality of patients’ life.      
 
Adrenergic receptor blocking drugs (β-blockers)
Adrenergic receptor blocking drugs are capable of selectively bind to β-adrenergic receptors, thus inhibiting the binding of antagonism neurotransmitters and catecholamine to the receptor. This in turn prevents its agonist action towards the β receptor. By inhibiting the β receptor blockers, adrenergic receptors could slow down heart rate, decrease myocardial contractility, reduce cardiac output, and reduce the peripheral blood flows during systolic ejection period, thereby reducing systolic blood pressure. Meanwhile, blockers could lead to relaxation of small arteries and small veins vascular of smooth muscle, reduce peripheral vascular resistance, and significantly lower diastolic blood pressure. It can be used as a therapeutic drug of choice for patients with mild to moderate hypertension, especially for those with angina pectoris, myocardial infarction, or those accompanied by rapid heart rhythms. These drugs can cause abnormal lipid metabolism, in which, its long-term use can increase triglycerides, lower serum HDL, thus increasing the total cholesterol to HDL ratio. Bisoprolol^[43] and atenolol^[44] drugs have been reported for the improvement of patients’ quality of life. However, large doses of metoprolol (200 mg/day) have shown a negative impact on quality of patients’ life^[49]. In addition, propranolol also has been considered to have a negative impact.
 
Converting enzyme inhibitors and AngII antagonists
The main antihypertensive mechanism of ACEI[H4]  is: (1) Inhibiting circulation of local tissue converting enzyme (kininase Ⅱ), so that ACEI cannot be converted to angiotensin (ATⅡ), thus leading to vasodilation and reduction of blood pressure. (2) Reducing the degradation of bradykinin (BK), which subsequently raises the BK level in the body, increases dilation of blood vessels, and thus lowers blood pressure. ACEI’s biggest feature is that it reverses remodeling of left ventricular and vascular hypertrophy, which in turn increases renal blood flow and glomerular filtration rate, reduces proteinuria during kidney damage, and delays the progress of kidney damage for diabetes patients. It has no adverse effects on the level of blood sugar, cholesterol, and uric acid, which ultimately improves the quality of patients’ life and thus, reduces mortality.
The main side effects are cough, skin rashes, and a small number of patients may experience abnormal taste sensation and deterioration of renal function; whereby angioedema are rare, but can endanger the lives of patients. Through blocking of the ATl mediated vascular smooth muscle contractile response, ARB[H5]  achieved the lowering of blood pressure by decreasing the peripheral resistance. In reality it blocks the action of all AngⅡat the receptor level, thereby achieving a more complete suppression of the adverse effects of AngⅡthan ACEI inhibitors. ARB has a direct protective effect on hypertension patients’ heart, blood vessels and kidneys, and this protective effect does not depend on the antihypertensive effect of the drug. Thus, increasing the clinical value of blockers as antihypertensive drug, especially for high-risk patients with hypertension^[50,51]. These drugs have fewer side effects such as cough. Hence, it is suitable especially for patients who cannot tolerate the side effects of cough caused by ACEI. Captopril has a good impact on patients' mental state (depression, anxiety, mood swings), and rarely discontinued due to its side effects, and can significantly improves the overall feeling and life satisfaction of patients. Naphthalene and enalapril drugs^[44,46,48] are conducive to improve patient QOL. Hypertension patients who consumed losartan for 12 weeks experienced an improvement in the overall sense of well-being^[45].
 
Diuretics and others
The main role of diuretics is to decrease blood volume, thereby reducing both ventricular end-diastolic volume and cardiac preload. On the other hand, while reducing cardiac output, diuretics may reduce systolic peripheral and in turn lower systolic blood pressure. It is suitable for hypertension patients with congestive heart failure, edema and renal function insufficiency caused by other reasons. It can reduce the incidence and mortality rate due to cardiovascular disease^[52] and left ventricular hypertrophy symptom^[53].
However, it can increase electrolyte imbalance and the risk of abnormal lipid metabolism, such as loss of potassium ions, lead to weakness, fatigue, convulsions and other symptoms. It also increases the Ca²⁺ reabsorption and forms hypercalcemia. It also elevated blood sugar in diabetic patients and plasma cholesterol levels. There will be a handful of people experiencing neutropenia and gastrointestinal reactions. When used alone, methyldopa had no significant effect on QOL, but the addition of thiazide diuretics and long-term (more than 6 months) usage has a negative impact on the overall health sense. While hydrochlorothiazide and doxazosin are not compromising the quality of patients’ life, hydrochlorothiazide improved quality of life significantly. A large number of studies  suggested that, the current drugs for the treatment of hypertension in patients are generally well-tolerated, and its adverse effects are often due to overdose^[46]. After 6–8 months of medication, the quality of patients’ life was improved by about 2%, with a variation margin of 5%. The authors believed that while the magnitude of improvement is small, it is still a good representation of patient conditions.[H6] 
 
The impact of drugs on quality of life is related to the quantity of drug taken
Klocek and Kawecka-Jaszcz found that the quality of life for patients with untreated hypertension was lower than in healthy people, but higher than the treated hypertension patients^[53]. Quality of patient’s life and quantity of medication is inversely related, as such, patients receiving with 4 types of antihypertensive drugs experienced significantly lower quality of life than those receiving with one-, two-, and three types of antihypertensive drugs. A population-based study using a community sample found that hypertension patients who were taking fewer drugs had higher quality of life^[55]. This may be related to the severity of the patients’ hypertension. Patients with mild case of hypertension can control blood pressure without medication or with one kind of drug. However, patients with severe hypertension need to take multiple medications to regulate their blood pressure. A large number of studies suggested that the drugs currently used to treat hypertension are generally well-tolerated by patients, and its adverse effects are often due to overdose. A number of drugs could improve the quality of life, but the extent of improvement in quality of life is less. Croog et al. found that after 6–8 months of medication, the quality of life was improved by about 2%, with a variation margin of 5%. The authors believed that while the magnitude of improvement is small, it is still a good representation of patient conditions.[H7] 
 
The clinical significance of drug therapy on the quality of life of the hypertension patients
Currently, there are still conflicts regarding the impact of drug therapy on the quality of life in patients with hypertension. However, clinical work still needs to be carried out in order to treat hypertension patients. A multi-center, randomized, and double-blind clinical trial known as SCOPE  study was conducted in 2003^[56]. Through studies of more than 5000 cases of patients with hypertension, Chakan candesartan of the prognosis and cognitive function of antihypertensive therapy in elderly patients with hypertension (70 to 89 years) was investigated. It was the first study that provides the basis for the treatment of the elderly and very old patients with hypertension. It included the use of general mental health index scale (PGWB), subjective symptoms assessment scale (SSA-P) and the European Quality of Life Assessment Scale (EuroQoL) for measuring health-related quality of life. A comparison between the candesartan and the control group showed that the candesartan group scored higher on each of the quality of life’s index. In addition, the patients in candesartan group had a significantly lower blood pressure than those in control group. The improvement of the quality of patients’ life in the candesartan group could be attributed to the drug induced in lowering of blood pressure.
The mechanism, in which, drugs impacts on quality of life is still unclear. Testa et al. observed that even with the same effect and the same mechanism of action, captopril led to a greater enhancement of QOL compared to enalapril. It may be related to their respective in vivo distribution. RAS system acting drugs, such as ACEI and AngIl blockers, have anxiolytic effects and can improve cognitive function. The encouraging preliminary results reported in June 1998 by the HOT[H8]  trial ruled out a past misconception: that intensive lowering of blood pressure level has a significant adverse impact on QOL. The HOT study showed that lower blood pressure was more conducive to improve the quality of life. Thus, there is no doubt on the antihypertensive treatment because of its neutral effect on quality of life and to the elderly patients who receive antihypertensive treatment.
       In conclusion, hypertension is one of the important stroke risk factors that could be intervened, and it is a common complication of acute stroke, in which, the two are closely related. Since antihypertensive treatment plays an important role in secondary stroke prevention, treatment should be effective in controlling blood pressure levels. At the same time, it should prevent and reverse organ damage in patients, maintain the quality of patients’ life and reduce the burden on patients and society. Within the realm of clinical practice, the characteristics of various types of antihypertensive drugs should be fully understood. In combination with specific circumstances of the patient, a comprehensive assessment of the reasonable control of blood pressure should be implemented in order to improve the quality of patients’ life.
 
Author contributions
Fangfang Zhu prepared the manuscript.
 
Conflict of interest
The author declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article.
References
1.      Verdecchia P, Angeli F, Borgioni C, Gattobigio R, Reboldi G. Ambulatory blood pressure and cardiovascular outcome in relation to perceived sleep deprivation. Hypertension 2007; 49: 777–783. doi.org/10.1161/01.HYP.0000258215.26755.20.
2.      Rosendorff C, Black HR. Evidence for a lower target blood pressure for people with heart disease. Curr Opin Cardiol 2009; 24(4): 318–324. doi.org/10.1097/HCO.0b013e32832bfb48.
3.      Zhao M, Fang X. Antihypertensive therapy and cerebral stroke secondary prevention[H9] . Chinese Journal of Hypertension 2008; 16(8): 685–687.
4.      Xie P. The prevention of hypertension and cerebral stroke[H10] . Tiantan International Conference on Cerebrovascular Disease 2008; 30–31.
5.      Huang Z, Yang H, Kaixian NA. Risk factors analysis of hypertensive stroke patients[H11] . Modern Journal of Integrated Traditional Chinese and Western Medicine 2009; 18(31): 3813–3814.
6.      Pang H, Fu Q, Huang YJ, Jiang SZ, Li XD. Survey on the 10-year probability of stroke for hypertension. Chinese Journal of Cerebrovascular Diseases 2012; 6(5): 261–265.
7.      Antikainen RL, Moltchanov VA, Chukwuma SC, Kuulasmaa KA, Marques-Vidal PM, et al. Trends in the prevalence, awareness, treatment and control of hypertension: the WHO MONICA project. Eur J Cardiovasc Prev Rehabil 2006; 13(1): 13–29. doi.org/10.1097/01.hjr.0000185977.82383.b5.
8.      Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, et al. AHA/ASA guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. Stroke 2006; 37: 577–617. doi.org/10.1161/01.STR.0000199147.30016.74.
9.      Leonardi-Bee J, Bath PMW, Phillips SJ, Sandercock PAG, IST Collaborative Group. Blood pressure and clinical outcomes in the international stroke trial. Stroke 2002; 33: 1315–1320. doi.org/10.1161/01.STR.0000014509.11540.66.
10.  Feng S, Zhao X, Liu Y, Huo H. Cox regression analysis on risk factors for recurrent stroke.  Med J West China 2013; 25(6): 857–859. doi:10.3969/j.issn.1672—3511.2013.06.019.
11.  Wang W, Deng Q, He H, Ma L. Clinical evidence of blood pressure lowering therapy on the secondary prevention of stroke. Chinese J Evidence-Based Medicine 2004; 4(5): 355–358.
12.  Vasan RS, Beiser A, Seshadri S, Larson MG, Kannel WB, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: the Framingham heart study. JAMA 2002; 287(8): 1003–1010. doi.org/10.1001/jama.287.8.1003.
13.  Bai X. Primary prevention of hypertension and stroke. Medical Innovation of China 2009; 6(7): 17. doi:10.3969/j.issn.1674-4985.2009.07.008.
14.  Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update. Circulation 2007; 116: e391–e413. doi.org/10.1161/CIRCULATIONAHA.107.183689.
15.  Anderson CS, Huang Y, Arima H, Heeley E, Skulina C, et al. Effects of early intensive blood pressure-lowering treatment on the growth of hematoma and perihematomal edema in acute intracerebral hemorrhage: the intensive blood pressure reduction in acute cerebral haemorrhage trail (INTERACT). Stroke 2010; 41(2): 307–312. doi.org/10.1161/STROKEAHA.109.561795.
16.  Schellinger PD, Fiebach JB, Hoffmann K, Becker K, Orakciolu B, et al. Stroke MRI in intracerebral hemorrhage: is there a perihemorrhagic penumbra?. Stroke 2003; 34: 1674–1679. doi.org/10.1161/01.STR.0000076010.10696.55.
17.  Broderick JP, Diringer MN, Hill MD, Brun NC, Mayer SA, et al. Determinants of intracerebral hemorrhage growth: an exploratory analysis. Stroke 2007; 38: 1072–1075. doi.org/10.1161/01.STR.0000258078.35316.30.
18.  Jauch EC, Lindsell CJ, Adeoye O, Khoury J, Barsan W, et al. Lack of evidence for an association between hemodynamic variables and hematoma growth in spontaneous intracerebral hemorrhage. Stroke 2006; 37: 2061–2065. doi.org/10.1161/01.STR.0000229878.93759.a2.
19.  Geeganage CM, Bath PMW. Interventions for deliberately altering blood pressure in acute stroke. Stroke 2009; 40(5): e390–e391. doi:10.1161/STROKEAHA.108.535849.
20.  Liu GZ, Xu CM, Li WJ. The effect of blood pressure control for hypertensive intracerebral hemorrhage. Chinese Journal of Medical Recapitulate 2011; 17(17): 2708–2709.
21.  Wityk RJ. The management of blood pressure after stroke. Neurologist 2007; 13(4): 171–181. doi.org/10.1097/NRL.0b013e318068b63e.
22.  Sare GM, Gray LJ, Wardlaw J, Chen C, Bath PMW, et al. Is lowering blood pressure hazardous in patients with significant ipsilateral carotid stenosis and acute ischaemic stroke? Interim assessment in the “efficacy of nitric oxide in stroke” trial. Blood Press Monit 2009; 14(1): 20–25. doi.org/10.1097/MBP.0b013e32831e30bd.
23.  Adams Jr HP, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, et al. AHA/ASA guideline: guidelines for early management of adults with ischemic stroke. Stroke 2007; 38: 1655–1711. doi.org/10.1161/STROKEAHA.107.181486.
24.  The Chinese Medical Association neuropathy division cerebrovascular disease study group, acute ischemic stroke treatment guidelines writing group. Chinese acute ischemic stroke treatment guidelines 2010; 43: 1–8.[H12] 
25.  Robinson TG, Potter JF, Ford GA, Bulpitt CJ, Chernova J, et al. Effects of antihypertensive treatment after acute stroke in the continue or stop post-stroke antihypertensives collaborative study (COSSACS): a prospective, randomized, open, blinded-endpoint trial. Lancet Neurol 2010; 9(8): 767–775. doi.org/10.1016/S1474-4422(10)70163-0.
26.  Underwood M, Lobo BL, Finch C, Wang J. Overuse of antihypertensives in patients with acute ischemic stroke. South Med J 2006; 99(11): 1230–1233. doi.org/10.1097/01.smj.0000232214.06335.ca.
27.  Schrader J, Lüders S, Kulschewski A, Berger J, Zidek W, et a1. The ACCESS study-evaluation of acute candesartan cilexetil therapy in stroke survivors. Stroke 2003; 34(7): 1699–1703. doi.org/10.1161/01.STR.0000075777.18006.89.
28.  Aslanyan S, Fazekas F, Weir CJ, Horner S, Lees KR, et a1. Effect of blood pressure during the acute period of ischemic stroke on stroke outcome. Stroke 2003; 34(10): 2420–2425. doi.org/10.1161/01.STR.0000091233.04524.0C.
29.  Nie D, Li C, Xie Q, Xie K. The effect of blood pressure lowering treatment during the acute period of ischemic stroke on stroke outcome. Chinese Journal of Stroke and Nervous Diseases 2007; 14(2): 89–92.
30.  Pan G, Gan Y. Effect of antihypertensive treatment of acute cerebral infarction on prognosis. Modern journal of integrated traditional Chinese and western medicine 2008; 17(24): 3788–3789. doi:10.3969/j.issn.1008-8849.2008.24.039.
31.  Luo H, Yu W, Li SB, Zhang H, Ling W. Post acute stroke antihypertensive treatment can reduce mortality. Chinese Journal of Practical Medicine 2009; 4(21): 56–57.[H13] 
32.  Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, et al. AHA/ASA guidelines: guidelines for the prevention of stroke in patients with stroke or transient ischemic attack. Stroke 2011; 42(1): 227–276. doi.org/10.1161/STR.0b013e3181f7d043.
33.  Bejan-Angoulvant T, Saadatian-Elahi M, Wright JM, Schron E, Lindholm LH, et al. Treatment of hypertension in patients 80 years and older: the lower the better? A meta-analysis of randomized controlled trials. J Hypertens 2010; 28(7): 1366–1372. doi.org/10.1097/HJH.0b013e328339f9c5.
34.  Chinese Hypertension League, The Ministry of Health Cardiovascular Disease Prevention Research Center, Chinese Hypertension Prevention Guide Revision Committee. Chinese Hypertension Prevention Guide (2005 revised edition). J Hypertens 2005; 13 Suppl: 3–41.[H14] 
35.  Adams R, Albers G, Alberts M, et a1. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke 2008; 39: 1647–1652. doi.org/10.1161/STROKEAHA.107.189063.
36.  Liu L, Wang Z, Gong L, Zhang Y, Thijs L, et al. Blood pressure reduction for the secondary prevention of stroke: a Chinese trial and a systematic review of the literature. Hypertens Res 2009; 32(11): 1032–1040. doi.org/10.1038/hr.2009.139.
37.  Boutitie F, Oprisiu R, Achard JM, Mazouz H, Wang J, et al. Does a change in angiotensin II formation caused by antihypertensive drugs affect the risk of stroke? A meta-analysis of trials according to treatment with potentially different effects on angiotensin II. J Hypertens 2007; 25(8): 1543–1553. doi.org/10.1097/HJH.0b013e32814a5ae5.
38.  Rothwell PM. Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension. Lancet 2010; 375(9718): 938–948. doi.org/10.1016/S0140-6736(10)60309-1.
39.  Webb AJS, Fischer U, Mehta Z, Rothwell PM. Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis. Lancet 2010, 375(9718): 906–915. doi.org/10.1016/S0140-6736(10)60235-8.
40.  Gao Q. Determination of quality of life. Chinese Journal of Rehabilitation Medicine 1995; 10: 240–243.[H15] 
41.  Van Bortel LMAB, Breed JGS, Joosten J, Kragten JA, Lustermans FAT, et al. Nebivolol in hypertension: a double-blind placebo-controlled multicenter study assessing its antihypertensive efficacy and impact on quality of life. J Cardiovasc Pharmacol 1993; 21(6): 856–862. doi.org/10.1097/00005344-199306000-00002.
42.  Turner RR. Role of quality of life in hypertension therapy: implication for patient compliance. Cardiology 1992; 80(1): 11–22. doi.org/10.1159/000175043.
43.  de Hoon JNJM, Vanmolkot FHM, van de Ven LLM, Van Bortel LMAB. Quality of life comparison between bisoprolol and nifedipine retard in hypertension．Cardiovasc Drugs Ther 1997; 11(3): 465–470. doi.org/10.1023/A:1007701606758.
44.  Grimm Jr RH, Grandits CA, Cutler JA, Stewart AL, McDonald RH, et al. Relationships of quality-of-life measures to long-term lifestyle and drug treatment in the treatment of mild hypertension study. Arch Intern Med 1997; 157(6): 638–648. doi:10.1001/archinte.1997.00440270080007.
45.  Dahlöf B, Lindholm LH, Carney S, Pentikäinen P, Östergren J, et al. Main results of the losartan versus amlodipine (LOA) study on drug to lerability and psychological general well-being. J Hypertens 1997; 15(11): 1327–1335.
46.  Grimm RHJ, Gutter JA. For the FOMHS Research Group relations of QOL measures to long-term life-style and drug treatment in TOMHS[J]. Arch Intern Med, 1997, 57: 638-648.[H16] 
47.  Chan P, Lin CN, Tomlinson B, Lin TH, Lee YS. Additive effects of diltiazem and lisinopril in the treatment of elderly patients with mild-to-moderate hypertension. Am J Hypertens 1997; 10(7): 743–749. doi.org/10.1016/S0895-7061(96)00060-X.
48.  Gralec M, Piusińska-Macoch A, Cholewa M, Sułek K. Changes in the quality of life influenced by treatment of primary arterial hypertension. Pol Merkur Lekarski 1997; 2(7): 28–31.
49.  Dahlöf C, Dimegnäs E, Kendall M, Wiklund I. Quality of life in cardiovascular disease; emphasis on beta-blocker treatment. Circulation 1991; 84(6 Suppl): 108–118.
50.  Arici M, Erdem Y. Dual blockade of the renin-angiotensin system for cardiorenal protection: an update. Am J Kidney Dis 2009; 53(2): 332–345. doi.org/10.1053/j.ajkd.2008.11.021.
51.  Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and the National High Blood Pressure Education Program Coordinating Committee. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157(21): 2413–2446. doi.org/10.1001/archinte.1997.00440420033005.
52.  Freised, Yao CF. Modern drugs and anti-hypertensive drug treatment modalities. Chinese Journal of Foreign Medical Sciences (Section of Pharmacy) 1997; 24(3): 154–158.
53.  Klocek M, Kawecka-Jaszcz K. Quality of life in patients with essential arterial hypertension. Przegl Lek 2003; 60(2): 92–106.
54.  Lawrence WF, Fryback DG, Martin PA, Klein R, Klein BEK. Health status and hypertension: a population-based study. J Clin Epidemiol 1996; 49(11): 1239–1245. doi.org/10.1016/S0895-4356(96)00220-X.
55.  Degl’Innocenti A, Elmfeldt D, Hofman A, Lithell H, Olofsson B, et al. Health-related quality of life during treatment of elderly patients with hypertension: results from the study on cognition and prognosis in the elderly (SCOPE). J Hum Hypertens 2004; 18: 239–245. doi.org/10.1038/sj.jhh.1001657.