Prevalence of risk factors in patients with spontaneous intracerebral hemorrhage in Damascus _ Syria: a retrospective cross-sectional study

doi:10.21203/rs.3.rs-5188813/v1

Objectives: This study aims to determine the prevalence of risk factors among patients with spontaneous intracerebral hemorrhage in Syrian society and the variations in their
distribution according to age and gender.

Methods: This study is a retrospective cross-sectional study, patients data was collected by reviewing the medical records of patients from Al-Assad University Hospital, Al-Mouwasat University Hospital, Children's University Hospital, and Damascus Hospital.

Cross-tabulation tables and the Chi-square test were used to show the relationship between gender/age and the prevalence of risk factors, demonstrate statistical significance and calculate P-value.

Results: From a total of 194 patients included in the study, there were 123 males, accounting for 63.4% of the patients, while there were 71 females, accounting for 36.6%.

The most common risk factor among intracerebral hemorrhage patients was hypertension at 44.8% of the total patients, followed by antithrombotic use at 25.8%, smoking at 19.1%, diabetes at 15.5%, and hematological diseases making up 9.3% of the patients, whereas in age groups under 10 years, various hematological diseases were the most prevalent risk factors at 42.5%, followed by prematurity at 27.5%, and hyaline membrane disease at 15%.

The study showed no statistically significant differences in the distribution of risk factors between males and females except for smoking. However, the results revealed a significant difference in the distribution of risk factors according to age for Smoking, hypertension, antithrombotic use, diabetes, arteriovenous malformation, hyaline membrane disease, hematological diseases, and prematurity(p<0.05).

Conclusion: The study showed that hypertension and antithrombotic use are the most important risk factors for intracerebral hemorrhage, so controlling arterial pressure and periodic tests such as (platelet count/PT/PTT) are gold roles in preventing intracerebral hemorrhage.

Hospital Medicine

Intracerebral hemorrhage

risk factors

Damascus

hypertension

prematurity

antithrombotic use

Intracerebral hemorrhage (ICH), a subtype of stroke, is a devastating condition whereby a hematoma is formed within the brain parenchyma with or without blood extension into the ventricles.⁽¹⁾ Intracerebral hemorrhage can occur as a complication of a pre-existing lesion, such as vascular malformation or tumor, which is then referred to as secondary intracerebral hemorrhage. Primary intracerebral hemorrhage refers to intracerebral hemorrhage in the absence of a single clear underlying lesion and is the most frequent type of intracerebral hemorrhage.⁽²⁾ The initial injury mechanism in ICH is compressing brain parenchyma by hematoma’s mass effect, resulting in physical disruption of parenchymal architecture.⁽³⁾

ICH accounts for 15–20% of stroke cases, with an annual incidence of 24.3 per 100,000 population, and the disability rate can reach as high as 75%. The highest incidence of ICH occurs in the age groups of 50–59 and 60–69. Each year, approximately 2.8 million people die of intracerebral hemorrhage (ICH) worldwide^(4_6). For example, in Korea, intracerebral hemorrhage is the second leading cause of death after cancer and the first cause of death due to single organ disease.⁽⁷⁾

Noncontrast computerized tomography (NCCT) is a fast technique with excellent sensitivity for identifying acute ICH, and given its wide availability is considered the gold standard for the diagnosis of ICH.⁽⁸⁾

The outcome of ICH is variable, depending on hematoma volume, location, extension to ventricles, and other factors.⁽³⁾ Hematoma expansion translates into higher mortality and functional dependence over long-term follow-up. Low and high hemoglobin concentrations on admission indicated poor outcomes in young adult patients with ICH, the survival analysis showed even mild to moderate anemia correlated with higher mortality.^(9_10)

Modifiable risk factors include hypertension, cigarette smoking, excessive alcohol consumption, decreased low-density lipoprotein cholesterol, low triglycerides and drugs including antithrombotic, antithrombotic agent, and sympathomimetics. Non-modifiable risk factors include old age, male sex, CAA (cerebral amyloid angiopathy), and Asian ethnicity.⁽³⁾

Hypertension is a well-known risk factor for intracerebral hemorrhage (ICH) and Primary ICH in most cases is associated with chronic hypertension. From a pathological point of view, hypertension can cause arteriolosclerosis, an accumulation of degenerative material in the tunica intima (inner layer) of artery walls. Subsequently, the form of the disease are characterized by fibrinoid necrosis, lipohyalinosis, microatheroma, and microaneurysms.^(11_13)

High alcohol intake is an important risk factor for development of liver diseases and alcohol intake may further induce hypertension. In addition, alcohol intake is associated with changes in the coagulation system and may also affect the integrity of cerebral vessels.⁽¹⁴⁾

Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH).⁽¹⁵⁾

Decreased GFR is a strong risk factor for hemorrhagic, but not ischemic stroke. Of the many mechanisms underlying cerebrovascular disease, small vessel microangiopathy would presumably be the type with the strongest association with CKD, because the primary underlying pathology for both disease entities is thought to be the induction of endothelial permeability because of high volume blood flow to these low-resistance-end arterial organs (brain and kidney).^(16_17)

Current smoking and diabetes mellitus are weak risk factors, and data for hypercholesterolemia were conflicting. However, low cholesterol levels have been thought to decrease vessel resistance to rupture, as cholesterol is essential for normal membrane fluidity.^(18_19)

Spontaneous intracerebra hemorrhage accounts for about 50% of stroke in children whereas in adults it accounts for only about 15%.It is known from other studies that prematurity infants who required assisted ventilation were at great risk for developing intracranial hemorrhage.^(20_21)

The distribution of the major modifiable risk factors for intracerebral hemorrhage (ICH) changes rapidly and Increased knowledge of the risk factors related to sICH (spontaneous intracerebral hemorrhage) will improve the prognosis of patients,^(22_23) to this reasons this study has a great importance.

Firstly, an ethical approval was obtained from the Biomedical Research Ethics Committee (BMREC) at Damascus University with ID number (MD-020624-243), as well as other approvals were obtained from relevant hospitals adminstrations.

This study is a retrospective cross-sectional study, patients data was collected by reviewing the medical records of patients from Al-Assad University Hospital, Al-Mouwasat University Hospital, Children's University Hospital, and Damascus Hospital who were diagnosed with intracerebral hemorrhage through a CT scan without contrast or brain echo for newborns admitted to Children's University Hospital. Patients with doubtful diagnosis of intracerebral hemorrhage, incomplete information in their records, or missing CT scan reports were excluded, as well as patients who were diagnosed with traumatic intracerebral hemorrhage.

Data was recorded in Microsoft Excel program including age, gender, and various potential risk factors such as smoking, alcohol consumption, hypertension, antithrombotic use, diabetes, chronic kidney disease, primary and secondry tumors, aneurysms, moyamoya disease, arteriovenous malformations (AVMs), prematurity, hyaline membrane disease, hematological diseases through medical and drug history.

IBM SPSS Statistics version 23 was used for data analysis and cross-tabulation tables were used to show the relationship between gender/age and the prevalence of risk factors using the Chi-square test to show statistical significance and calculate P-value, and all statistical operations were conducted with (CI:95% and p:0.05). Microsoft Excel program was used to create tables and figures.

From a total of 194 patients included in the study, there were 123 males, accounting for 63.4% of the patients, while there were 71 females, accounting for 36.6% of the total patients. The distribution of patients by age was as follows: 40 patients under the age of 10, accounting for 20.6%, 16 patients aged 11 to 30, accounting for 8.2%, 72 patients aged 31 to 60, accounting for 37.1%, and 66 patients over the age of 60, accounting for 34% as shown in figure(A).

The number of patients with intracerebral hemorrhage without any known risk factor was 38 patients, accounting for 19.6%. Those with only one risk factor were 77 patients, accounting for 39.7%, while those with two risk factors were 47 patients, accounting for 24.2%, patients with three risk factors were 27, accounting for 13.9%, and those with four risk factors were 5, accounting for 2.6%.

The most common risk factor among intracerebral hemorrhage patients was hypertension at 44.8% of the total patients, followed by antithrombotic use at 25.8%, smoking at 19.1%, diabetes (type I and II) at 15.5%, and hematological diseases (bacteraemia, DIC, hemophilia, hemorrhagic disease in the newborn, and leukemias) making up 9.3% of the patients. Other risk factors such as alcohol consumption, chronic kidney disease, aneurysms, arteriovenous malformations, moyamoya disease, prematurity, hyaline membrane disease, and tumors were present in fewer patients as shown in Figure(B).

The study showed no statistically significant differences in the distribution of risk factors between males and females(p > 0.05)

, while there was a difference in the prevalence of smoking among patients with intracerebral hemorrhage, with 24.4% of males and 9.9% of females being smokers(p < 0.05). Hypertension, antithrombotic use, smoking, and diabetes remained the most prevalent risk factors in both genders.

Table(A) and figure(B) illustrate the distribution of risk factors by gender.

The study results showed a significant difference in the distribution of risk factors according to age for Smoking, hypertension, antithrombotic use, diabetes, arteriovenous malformation, hyaline membrane disease, hematological disaeses, and prematurity were statistically significant in terms of age (p < 0.05), but alcohol consumption, chronic kidney disease, tumors, moyamoya disease, and aneurysms did not have a statistically significant association with age(p > 0.05). Table(B) and figure(C) show the distribution of risk factors by age in patients with intracerebral hemorrhage.

In the age group of 31 to 60 years, hypertension was the most prevalent risk factor accounting for 58.3%, followed by smoking at 23.6%, and antithrombotic use at 22.2%. In the age group over 60 years, hypertension remained at the forefront of risk factors accounting for 68.2%, followed by antithrombotic use at 47%, and smoking at 24.2%. In age groups under 10 years, various hematological diseases (such bacteraemia, DIC, hemophilia, hemorrhagic disease in the newborn, and leukemias) were the most prevalent risk factors at 42.5%, followed by prematurity at 27.5%, and hyaline membrane disease at 15%.

This is the first study of its kind in Syria to determine the distribution of intracerebral hemorrhage according to age and gender, and to explain the differences in the prevalence of risk factors according to age and gender.

In this study, we documented an increase in intracerebral hemorrhage with advancing age in both genders, particularly in ages over 30 and this is consistent with a previous study which found that the rate of intracerebral hemorrhage in young people increases with the increasing of age,⁽²⁴⁾ we also observed a peak in injury occurrence among newborns, especially in premature infants, which is a prominent result that was not indicated by previous studies.

We did not observe a significant statistical difference in the prevalence of risk factors between males and females except for smoking, which was higher among males; this is contrary to a previous population-based study conducted in France, which showed that smoking rates remained stable during the study period in France among men and women aged 15 to 75 years but increased in women aged 50–75 years.⁽²⁵⁾

Hypertension, which accounted for 44.8%, antithrombotic use at 25.8%, and smoking at 19.1% were the most prevalent and important risk factors among all patients, as well as patients over 60 years old, this is consistent with previous studies indicating that hypertension is a major risk factor for intracerebral hemorrhage in the general population. Regarding smoking, most previous studies did not find any statistically significant relationship between cigarette smoking and intracerebral hemorrhage.^(26_27) Other risk factors such as alcohol consumption, chronic kidney disease, aneurysms, and arteriovenous malformations were less prevalent. We also observed intracerebral hemorrhage occurrence in patients without any risk factors (19.6%).

In patients aged 31–60, hypertension, smoking, and antithrombotic use were the most prevalent in that order. In patients aged 11–30, smoking and arteriovenous malformations were the most important factors, as indicated in a previous study showing a higher rate of vascular malformations in the 20–29 age group compared to other age groups.⁽²⁴⁾ In patients younger than 10 years old, hematological diseases, prematurity, and hyaline membrane disease were the most prevalent risk factors.

In the end, this research was conducted in Damascus Governorate only, so this research must be expanded to the rest of the governorates to obtain more accurate results that represent the entire Syrian society.

The study showed that hypertension is an important factor for intracerebral hemorrhage and is the most common risk factor, which makes controlling arterial pressure an important role in preventing intracerebral hemorrhage, we also found a high incidence rate among those taking antithrombotics, so they must be taken Carefully to the extent required, while conducting periodic tests such as (platelet count/PT/PTT). In addition, Abstaining from smoking plays an important role in the primary prevention of intracerebral hemorrhage, as it is the third most common risk factor.

Ethical approval:

the ethical approval was obtained from the Biomedical Research Ethics Committee (BMREC) at Damascus University with ID number (MD-020624-243)

Funding sources:

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of interest:

We declare no competing interests.

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Table (A): distribution of risk factors according to gender

risk factors	count (N=194)		Percentage (%)		p-value
risk factors	male	female	male	female	p-value
smoking	30	7	24.4	9.9	p < 0.05
alcohol consumption	3	0	2.4	0	p > 0.05
hypertension	57	30	46.3	42.3	p > 0.05
antithrombotic drugs use	35	15	28.5	21.1	p > 0.05
diabetes	22	8	17.9	11.3	p > 0.05
CKD	7	2	5.7	2.8	p > 0.05
tumors	3	2	2.4	2.8	p > 0.05
hyaline membrane disease	3	3	2.4	4.2	p > 0.05
prematurity	6	5	4.9	7	p > 0.05
hematological diseases	13	5	10.6	7	p > 0.05
moyamoya	0	1	0	1.4	p > 0.05
AVMs	3	2	2.4	2.8	p > 0.05
aneurysms	5	5	4.1	7	p > 0.05

Table (B): distribution of risk factors according to age

	less than 10 years	from 11 to 30 years	from 31 to 60 years	above 60 years	p-value
smoking	0.0%	25.0%	23.6%	24.2%	p < 0.05
alcohol consumption	0.0%	0.0%	2.8%	1.5%	p > 0.05
hypertension	0.0%	0.0%	58.3%	68.2%	p < 0.05
antithrombotic drugs use	5.0%	6.3%	22.2%	47.0%	p < 0.05
diabetes	0.0%	0.0%	22.2%	21.2%	p < 0.05
CKD	0.0%	0.0%	6.9%	6.1%	p > 0.05
tumors	2.5%	6.3%	1.4%	3.0%	p > 0.05
hyaline membrane disease	15.0%	0.0%	0.0%	0.0%	p < 0.05
prematurity	27.5%	0.0%	0.0%	0.0%	p > 0.05
hematological diseases	42.5%	0.0%	0.0%	1.5%	p < 0.05
moyamoya	0.0%	0.0%	0.0%	1.5%	p > 0.05
AVMs	0.0%	18.8%	1.4%	0.0%	p < 0.05
aneurysms	2.5%	6.3%	9.7%	1.5%	p > 0.05

The authors declare no competing interests.

Prevalence of risk factors in patients with spontaneous intracerebral hemorrhage in Damascus _ Syria: a retrospective cross-sectional study

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Abstract

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Introduction

Methods

Results

Discussion

Conclusion

Declarations

References

Tables

Additional Declarations

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