DOI: https://doi.org/10.21203/rs.3.rs-2293057/v1
To investigate the risk factors and adherence to hypotensor and hypotensive effect of ischemic stroke patients with hypertension.
The study enrolled 613 ischemic stroke cases from 2020.1-2022.4 of inpatient department of LiYuan Hospital, Tongji Medical College, Huazhong University of Science and Technology. Data on the type of stroke, frequency, demographics, chronic diseases history, the presence of influence factors and antihypertensive therapy were obtained from the electronic medical record (EMR). We used logistics model to investigate the possible risk factors of ischemic stroke with hypertension, and calculated the population attributable risk proportion (PARP). We also investigate the adherence to hypotensor and hypotensive effect.
The average age of the 613 ischemic stroke patients was (71.07 ± 11.52) years old, 52.69% were males (323). In ischemic stroke patients, 78.79% had hypertension (483). According to the results of logistics model, ischemic stroke patients with diabetes had the highest risk to combine with hypertension, Odds Ratios (OR) was 2.83 (1.77 ~ 4.52). Considering the prevalence of each factor in ischemic stroke patients, Dyslipidemia had the highest PARP of 60.4% (95%CI:36.5%-76.8%). In ischemic stroke patients with hypertension, 89.44% (432/483) had taken hypotensors, 51.76% (250/483) met the required level.
There still were a large number of ischemic stroke patients with hypertension, a low rate of adherence to hypotensor and reaching the target.
Hypertension is a significant risk factor for ischemic stroke. Data has shown the prevalence of hypertension among Chinese is on the rise in recent years. In China, 23.2% (≈ 244.5 million) of the adult population ≥ 18 had hypertension, and 41.3% (≈ 435.3 million) had pre-hypertension according to the Chinese guideline1. The prevalence of hypertension continues to increase resulting to worse prognosis of ischemic stroke patients. So it is of great significance to investigate the risk factors of ischemic stroke patients combined with hypertension and provide effective intervention to reduce the occurrence of poor prognosis2. Studies have shown that antihypertensive therapy is an important secondary prevention for ischemic stroke patients combined with hypertension3. The high recurrence rate is closely related with low medication adherence rate4. Moreover, blood pressure is not monitored when many patients are taking hypotensive agents, hypotensive effect is not good5. So the research is to investigate the risk factors and adherence to antihypertensive agents and hypotensive effect of ischemic stroke patients combined with hypertension.
Retrospective data was obtained from EMR of LiYuan Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2020 to April 2022. All data include type of stroke, diagnosis date, frequency, gender, age, area, marital status, alcohol drinking, smoking, family history of stroke, Modified Rankin Scale score, intracranial and extracranial arteriostenosis, psychosis/great psychological pressure, chronic diseases history and antihypertensive therapy. The inclusion criteria: diagnosed with ischemic stroke by neurologist and all cases have complete clinical information, neurological examination, laboratory tests (blood biochemical examination) and demographic characteristics. The exclusion criteria: patients with cancer, severe head trauma, brain tumor, brain surgery, hydrocephalus, multiple sclerosis, central nervous system infections and other severe diseases. We recruited 658 ischemic stroke cases, 45 ischemic stroke patients were excluded because of incomplete information. Finally, 613 patients were enrolled.
1. Diabetes mellitus: HbA1c ≥ 6.5% OR FPG ≥ 126 mg/dl (7.0mmol/l) (Fasting is defined as no caloric intake for at least 8 h) OR 2-h plasma glucose ≥ 200 mg/dl (11.1mmol/l) during an OGTT OR random plasma glucose ≥ 200 mg/dl (11.1mmol/l) OR taking hypoglycemic drugs6.
2. Hypertension: Systemic blood pressure equal to or exceeding 140/90mmHg OR taking antihypertensive agents.
3. Dyslipidemia: Triglycerides ≥ 2.26mmol/l OR total cholesterol ≥ 6.22mmol/l OR LDL-C ≥ 4.14mmol/l OR HDL-C < 1.04mmol/l OR taking lipid regulating agents7.
4. Smoking: ≥1 cigarette per day in last 3 months8.
5. Alcohol drinking: ≥ 100mL spirit alcohol more than three times a week8.
6. Family history of stroke: ≥1 person has stroke in parents and compatriots.
7. Arial fibrillation (AF): AF was defined by either with history of persistent AF OR supported by past electrocardiogram (ECG)8.
8. Coronary atherosclerotic cardiopathy: Having typical symptoms or signs of myocardial ischemia OR chest CT showed calcified plaque in the coronary arteries OR supported by past ECG.
9. Intracranial and extracranial arteriostenosis: Intracranial and extracranial artery intimal thickening or plaque or stenosis was confirmed by color ultrasound or MRA or CTA or DSA.
10. Modified Rankin scale9:
|
0 |
no symptoms |
|---|---|
|
1 |
no significant disability, despite symptoms: Able to perform all usual duties and activities |
|
2 |
slight disability: Unable to perform all previous activities but able to look after own affairs without assistance |
|
3 |
moderate disability: Requires some help, but able to walk without assistance |
|
4 |
moderately severe disability: Unable to walk without assistance and unable to attend to own bodily needs without assistance |
|
5 |
severe disability: Bedridden, incontinent, and requires constant nursing care and attention |
|
6 |
dead |
11. Target blood pressure: SBP < 130mmHg and DBP < 80mmHg (< 140/80 in elderly patients)10.
12. Psychosis/great psychological pressure: Psychosis diagnosed by a psychiatrist OR the patients have sleep disorders, poor appetite, abnormal mood or other mental stress.
Statistical analysis was performed with SAS version 9.4 for Windows. The age distribution was normal, expressed as mean ± standard deviation; Categorical variables were expressed by rate/constituent ratio. The ischemic stroke patients were divided into case group and control group according to whether they were combined with hypertension, chi-square test was used for the distribution differences of risk factors among different groups, and pairwise comparisons within groups were performed. Risk factors included age, gender, area, marital status, diabetes mellitus, auricular fibrillation, dyslipidemia, transient ischemic attacks, smoking, alcohol drinking, family history of stroke, frequency, mRs score, coronary atherosclerotic cardiopathy, intracranial and extracranial arteriostenosis, chronic inflammation, psychosis/great psychological pressure. Variables were subjected to multivariate analysis with a logistic regression after univariate analysis. The presence or absence of hypertension (coded as 0 or 1, respectively.) was the dependent variable. An unconditional multiple logistic regression model was used to calculate odds ratios (OR) and 95% confidence interval (CI). Population attributable risk proportion was estimated for each risk factor. Antihypertensive medication adherence and blood pressure control rate were analyzed using the chi-square test. Significance was set at P < 0.05.
The mean age of 613 ischemic stroke patients was (71.07 ± 11.52) years old, 52.69% were males (323); In ischemic stroke patients, 78.79% had hypertension (483).
There were significant differences in the prevalence of hypertension among ischemic stroke patients in different regions, the prevalence of urban patients was higher than that of rural patients; ischemic stroke patients with diabetes mellitus, dyslipidemia, coronary atherosclerotic cardiopathy had higher risk to combine with hypertension; the prevalence of hypertension in patients with mRs score of 2 and above was higher than that in patients with mRs score of 1 (χ2 = 9.786, P = 0.002), detailed results are shown in Table 1.
|
Characteristics |
Ischemic stroke patients(n = 613) |
Combined with hypertension(n = 483) |
χ2 |
P |
|---|---|---|---|---|
|
Gender |
0.245 |
0.621 |
||
|
Male |
323(52.69) |
257(79.57) |
||
|
Female |
290(47.31) |
226(77.93) |
||
|
Age (years old) |
3.328 |
0.068 |
||
|
＜72 |
296(48.29) |
224(75.68) |
||
|
≥ 72 |
317(51.71) |
259(81.70) |
||
|
Area |
4.175 |
0.041 |
||
|
City |
564(92.01) |
450(79.79) |
||
|
Countryside |
49(7.99) |
33(67.35) |
||
|
Marital status |
3.576 |
0.311 |
||
|
Spinsterhood |
10(1.63) |
10(100.00) |
||
|
Married |
558(91.03) |
437(78.32) |
||
|
Losing a spouse |
42(6.85) |
33(78.57) |
||
|
Divorce |
3(0.49) |
3(100.00) |
||
|
Diabetes mellitusa |
233(38.01) |
206(88.41) |
20.960 |
＜0.0001 |
|
Atrial fibrillation |
57(9.30) |
48(84.21) |
1.104 |
0.293 |
|
Dyslipidemiaa |
537(87.60) |
438(81.56) |
18.396 |
＜0.0001 |
|
Had a TIA |
22(3.59) |
20(90.91) |
2.005 |
0.157 |
|
Smoking |
126(20.55) |
102(80.95) |
0.443 |
0.506 |
|
Alcohol drinking |
86(14.03) |
71(82.56) |
0.849 |
0.357 |
|
Family history of stroke |
97(15.82) |
79(81.44) |
0.484 |
0.486 |
|
Frequency |
0.329 |
0.567 |
||
|
1 time |
543(88.58) |
426(78.45) |
||
|
༞1 time |
70(11.42) |
57(81.43) |
||
|
mRs score |
10.799 |
0.005 |
||
|
0 |
5(0.82) |
3(60.00) |
||
|
1 |
133(21.70) |
92(69.17) |
||
|
≥ 2 |
475(77.48) |
388(81.68) |
||
|
Coronary atherosclerotic cardiopathy |
321(52.37) |
265(82.55) |
5.707 |
0.017 |
|
Intracranial and extracranial arteriostenosis |
357(58.24) |
288(80.67) |
1.807 |
0.179 |
|
Chronic inflammation |
221(36.05) |
168(76.02) |
1.592 |
0.207 |
|
Psychosis/great psychological pressure |
78(12.72) |
65(83.33) |
1.103 |
0.294 |
|
asubjects with missing data were not included in the statistical analysis;TIA: Transient Ischemic Attacks. |
||||
Multivariate analysis showed that ischemic stroke patients with diabetes, dyslipidemia had higher risk to combine with hypertension, their Odds Ratios (OR) were 2.83 (1.77 ~ 4.52) and 2.72 (1.59 ~ 4.63). Considering the prevalence of each influence factor in ischemic stroke patients, dyslipidemia had the highest PARP of 60% (95%CI: 37%−77%), the PARP for diabetes was 41% (23%−56%). Results of multiple logistic regression analysis are shown in Table 2.
|
Variables |
β-coefficients |
Standard errors |
Wald χ2 |
OR(95%CI) |
P |
PARP(95%CI) |
|---|---|---|---|---|---|---|
|
Gender |
||||||
|
Male |
||||||
|
Female |
0.017 |
0.21 |
0.007 |
1.02 (0.67, 1.54) |
0.934 |
0.01 (−0.18, 0.19) |
|
Age (years old) |
||||||
|
<72 |
||||||
|
≥72 |
0.382 |
0.209 |
3.351 |
1.47 (0.973, 2.21) |
0.067 |
0.19 (−0.02, 40.38) |
|
Diabetes mellitus |
||||||
|
No |
||||||
|
Yes |
1.040 |
0.239 |
18.951 |
2.83 (1.77, 4.52) |
< 0.0001 |
0.41 (0.23, 0.56) |
|
Dyslipidemia |
||||||
|
No |
||||||
|
Yes |
1.000 |
0.272 |
13.491 |
2.72 (1.59, 4.63) |
< 0.0001 |
0.60 (0.37, 0.77) |
|
OR: Odds Ratio; CI: Confidence Interval; PARP: Population Attributable Risk Percent;Factors included gender, age, region, diabetes mellitus, dyslipidemia, mRs score and coronary atherosclerotic cardiopathy. |
||||||
432 patients were taking blood pressure medication and 250 patients achieved standard blood pressure in 483 ischemic stroke patients with hypertension. The rate of medicine taking was 89.44%, the control rate was 51.76%. The oral mediation rate and the control rate increase with increasing age, their P value were 0.006 and 0.000. The results are shown in Table 3 and Table 4.
|
Variables |
Ischemic stroke patients with hypertension (n = 483) |
Taking hypotensive agents (n = 432) |
χ2 |
P |
|---|---|---|---|---|
|
Gender |
1.314 |
0.252 |
||
|
Male |
257(53.21) |
226(87.94) |
||
|
Female |
226(46.79) |
206(91.15) |
||
|
Age (years old) |
7.703 |
0.006 |
||
|
＜72 |
224(46.38) |
191(85.27) |
||
|
≥ 72 |
259(53.62) |
241(93.05) |
||
|
Area |
4.256 |
0.077 |
||
|
City |
450(93.17) |
406(90.22) |
||
|
Countryside |
33(6.83) |
26(78.79) |
||
|
Marital status |
2.536 |
0.469 |
||
|
Spinsterhood |
10(2.07) |
9(90.00) |
||
|
Married |
437(90.48) |
388(88.79) |
||
|
Losing a spouse |
33(6.83) |
32(96.97) |
||
|
Divorce |
3(0.62) |
3(100.00) |
|
Variables |
Ischemic stroke patients with hypertension (n = 483) |
Achieving the blood pressure standard (n = 250) |
χ2 |
P |
|---|---|---|---|---|
|
Gender |
0.539 |
0.463 |
||
|
Male |
257(53.21) |
129(50.19) |
||
|
Female |
226(46.79) |
121(53.54) |
||
|
Age (years old) |
13.260 |
＜0.0001 |
||
|
＜72 |
224(46.38) |
96(42.86) |
||
|
≥ 72 |
259(53.62) |
154(59.46) |
||
|
Area |
1.236 |
0.266 |
||
|
City |
450(93.17) |
236(52.44) |
||
|
Countryside |
33(6.83) |
14(42.42) |
||
|
Marital status |
4.279 |
0.233 |
||
|
Spinsterhood |
10(2.07) |
5(50.00) |
||
|
Married |
437(90.48) |
225(51.49) |
||
|
Losing a spouse |
33(6.83) |
20(60.61) |
||
|
Divorce |
3(0.62) |
0(0.00) |
The results show that the proportion of hypertension in ischemic stroke patients was 78.79%, which was slightly higher than the finding of CNSSS-based survey (71.8%)11. (CNSSS is Stroke Screening Survey in China). Data has shown that the prevalence of hypertension increased from 13.6% in 1991 to 23.2% in 20151.5.
Ischemic stroke patients with diabetes mellitus have the highest risk to combined with hypertension which suggests that controlling blood glucose can effectively reduce the risk of ischemic stroke in hypertensive patients. The mechanisms of stroke caused by diabetes include vascular endothelial dysfunction, early atherosclerosis, inflammation and thickening of capillary basement membrane12. Diabetic patients have more severe clinical symptoms and prognosis after stroke. The PARP value of dyslipidemia is the highest, indicating that the prevention or prompt treatment of dyslipidemia has obvious effects on reducing the burden of ischemic stroke combined with hypertension in the population, which suggests that the prevention of ischemic stroke in patients with hypertension should focus on blood lipids. Low levels of high-density lipoprotein, high levels of triglycerides and low-density lipoprotein are closely associated with atherosclerosis13. Atherosclerosis is a major cause of heart disease, peripheral vascular disease and stroke14. Blood lipid control can reduce the risk of ischemic stroke recurrence.
Longstanding hypertension can cause damage to vascular endothelial cells and deposition of lipoproteins and fibrin, leading to arteriosclerosis. The likelihood of complicated aortic atherosclerosis (protruding atheroma, ulcerated plaques, and mobile debris) increases by 43% for every 10mmHg increase in arterial pressure15. Atherosclerotic plaques can rupture and/or hemorrhage resulting in acute cerebrovascular occlusions, or release fragments that cause artery-to-artery embolism. This study based on hospital cases found that adherence rate to antihypertensive medication of ischemic stroke patients with hypertension was 89.44%, however according to the clinical guidelines, all ischemic stroke patients with hypertension should be treated with antihypertensive therapy to reduce the incidence of complications16. Therefore the adherence to antihypertensive agents needs to be further improved. Moreover, the rate of adherence to antihypertensive medication in ischemic stroke combined with hypertension was higher in this study than in community-based study (77.46%) 11, which shows that effective supervision is of great significance to improve the drug adherence rate. The rate of blood pressure control in ischemic stroke patients with hypertension is 51.76%, indicating that although some patients are taking antihypertensive drugs but have no effective monitoring. Lots of patients’ blood pressure is not up to the standard, which needs to be paid attention to.
Limitations of this study: First, the sample size was small, so the results were limited; Second, medication duration and dose were not considered in the evaluation of medication adherence; Third, this is a retrospective and single-institution study, so it is unreasonable to extrapolate the results to other centers, and a multicenter survey with large samples can be conducted in the future.
The incidence of hypertension in ischemic stroke patients is high; The adherence rate of hypotensor in ischemic stroke patients combined with hypertension was still not enough and the rate of reaching the standard blood pressure was low. Antihypertensive therapy can reduce stroke recurrence and improve clinical prognosis. Improving patients’ adherence to hypotensor and effectively monitoring blood pressure are the focus of secondary stroke prevention at present and in the future.
EMR: Electronic medical record; PARP: Popolation attributable risk proportion; OR: Odds ratio; CI: Confidence interval; mRs: Modified Rankin Scale; HbA1c: Glycosylated Hemoglobin, Type A1c; FPG: Fasting Plasma Glucose; OGTT: Oral Glucose Tolerance Test; HDL-C: High-Density Lipoprotein Cholesterol; LDL-C: Low-Density Lipoprotein Cholesterol; AF: Arial fibrillation; ECG: Electrocardiogram; CT: Computerized tomography; MRA: Magnetic resonance angiography; CTA: Computed tomography angiography; DSA: Digital substraction angiography; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; TIA: Transient ischemic attacks; CNSSS: Stroke Screening Survey in China.
Ethical approval and consent to participate
Ethical approval was waived by the local Ethics Committee of Li Yuan Hospital, Tongji Medical College, Huazhong University of Science and Technology in view of the retrospective nature of the study and all the procedures being performed were part of the routine care. The research has been performed in accordance with the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study.
Consent for publication
Not applicable
Competing interests
Conflict of interests: None
Funding
Financial support: None
Authors’ contributions
Data collection ,data analysis and article writing were completed by Zhiqian Han; Shourong Wei revised the article; Huang Yao and Liangmin Gan helped collect the data.
Acknowledgments
We thank the Emergency Department of LiYuan Hospital, Tongji Medical College, Huazhong University of Science and Technology for helping in data collection.
Availability of data and materials
Materials are available on request to the corresponding author.