To demonstrate the relation between stroke due to vascular insufficiency and elevated serum Gammaglutamyl transferase.
In this research 390 individuals were studied, 195 cases were patients who had first-ever event of acute
ischemic stroke within a day. Remaining 195 were controls who were healthy individuals who accompanied the patients
(within ± 5 years and of same sex). Frequency of raised GGTwas compared between both groups.
Out of this sample of 390 patients 88 (22.6%) had elevated GGT. 26.7% of patients (cases) and 18.5% subjects
(controls) had raised GGT (p value greater than 0.05). Odds ratio was 1.44 ((at 95% CI, 0.992 to 2.103). Sex, age,
smoking, BMI did not change outcome.
Hence we conclude that ischemic stroke and increased GGThas no association with each other
Stroke entails a high socioeconomic burden due to increased morbidity and mortality and more commonly affects elderly patients who comprise a continuously increasing proportion of the population in developed countries.(1, 2). The identification of risk predictors may help clinicians to triage patients at greater risk. (3, 4) Serum Gamma-glutamyl transferase (GGT) has been conventionally considered a marker of excessive alcohol intake and/or liver dysfunction. There is accumulating evidence suggesting a prognostic role of GGT in cardiovascular diseases (CVD) including stroke.(1, 2, 5)
Rationale of this study is that there is no local published literature available showing its association with stroke. The results of this study will help physicians to identify patients at higher risk for ischemic stroke hence better management and prevention.
OBJECTIVE:
To determine the association between ischemic stroke and raised serum Gamma-glutamyl transferase.
MATERIAL AND METHODS: It was a case- control study conducted at the Medical Emergency Department, Lahore Greneral Hospital, Lahore. It was conducted for six months from 24th May to 30th Nov 2020. It was a Non-probability/ purposive sampling. At 95 % confidence interval and 80% power of study, taking frequency of raised GGT in groups with and without ischemic stroke 28.8% vs 16.9%,(6) required sample size is 390 (195 in each group)
Age 40 – 80 years
Both Male or Female
Cases were patients with first-ever episode of acute ischemic stroke according to operational definition (determined by history and CT scan) presenting within 24 hours
Controls were healthy attendants of patients matched by age (within ± 5 years) and gender but without history of cardiovascular diseases i.e. ischemic heart disease, ischemic stroke and peripheral vascular disease
Recent surgery or trauma determined by history
Any liver disease determined by abnormal ALT and ultrasonography (coarse echo texture, hepatomegaly or fatty infiltration)
History of alcohol intake
Patients with chronic kidney disease (creatinine > 1.4 mg/dl)
Patients with history of previous stroke
195 consecutive cases with ischemic stroke presenting to emergency department of Lahore General Hospital were offered to be enrolled in the study. After explaining the purpose of study, informed consent was obtained from all patients. After matching for age and gender, 195 controls were enrolled preferably the accompanying healthy attendants of the patients. CT scan of brain was performed and diagnosis was confirmed. Under aseptic conditions, venous blood samples were obtained from cases at the time of presentation in emergency department for baseline laboratory examination. Serum Gamma-glutamyl transferase was measured by using standard chemical analyzer. Data was collected in a structured performa containing background information like age, sex and raised GGT. HbA1c > 7%, history of current smoking and presence of dyslipidemia were recorded additionally to cater for effect modification. Data was analyzed using SPSS version 25. Mean with standard deviation was calculated for quantitative variables like age and serum GGT and frequency and percentages in case of categorical variables like gender, raised GGT. Association was determined by measuring odds ratio in both groups. Data was stratified for effect modifiers using chi square test. A p value
In our study population 390 patients were included with mean age of 53.68 ± 9.47 ranged from 40 to 70 years.
277 patients (58.2%) in our study population were less than 55 years of age whereas 163 patients (41.8%) were either 55 years or more in age.
288 patients (73.8%) among our sampled population were male and remaining 102 patients (26.2%) were female.
Sampled population (n=390) were equally distributed between case and control groups.
Out of 390 patients 88 (22.6%) had raised GGT.
HbA1c level in 62 patients (15.9%) were above 7% while in rest of 328 patients (84.1%) it was below or equal to 7%.
27 patients (6.9%) were currently smoking while rest of 363 (93.1%) were non-smoker.
Among our sampled population only 59 patients (15.1%) were having dyslipidemia.
When we cross tabulated our study group (case & control) with raised GGT and applied Pearson chi square test, the results came out n0n-significant (p=0.053). Raised GGT was statistically equally distributed among cases and controls (26.7% v/s 18.5%).
When we stratified the cross tabulated group and raised GT with gender, Among male patients of cases and control group with raised GGT level showed up non-significant results (p=0.130), similarly non-significant results were seen in cases and controls of female patients. (p=0.246).
When we stratified the cross tabulated group and raised GGT with age group, in cases and control group of patients with age below 55 years showed up non-significant results (p=0.155), similar results were seen in cases and controls of age group above 55 years (p=0.053).
When we stratified the cross tabulated group and raised GT with HbA1c > 7% , patients of cases and control group with raised GGT level showed up non-significant results (p=0.644) among patients with HbA1c > 7% of sampled population.
When we stratified the cross tabulated group and raised GT with current smokers, Among patients with smoking habits of cases and control group with raised GGT level showed up non-significant results (p=0.596).
When we stratified the cross tabulated group and raised GT with dyslipidemia patients, cases and control group with raised GGT level in dyslipidemia patients showed that, there was not a single patients of dyslipidemia with no raised GGT.
In our study, 26.7% of cases and 18.5% of controls has raised gamma-glutamyl transferase. This result implies a higher frequency of raised gamma-glutamyl transferase in patients with first episode of ischemic stroke. These results are comparable with previous studies. In a study, percentage of stroke patients presenting with high [>27 IU/L) GGT levels was greater than controls (28.8% vs. 16.9%).
But contrary to previous studies, the difference was statistically non-significant (p value > 0.05). Odds ratio ranged from 0.992 to 2.103 (at 95% CI) and came out 1.44. It implies that raised GGT was equally distributed among cases and controls. In the previous study, compared to subjects with GGT levels in the lowest quartile, those within the highest quartile had a 4.7-times increase in the odds of experiencing an ischemic stroke (95% CI 2.39-9.11, p< 0.001). This association remained significant after controlling for all potential confounders (adjusted OR, 2.90, 95% CI, 1.35-6.27; p <0.007). 7 The difference may be secondary to sample size, sampling technique and socio demographic difference.
Limitation of current study includes
A small sample size for a relatively common phenomenon
Consecutive non probability sampling leading to non-generalization of results
A single center study and population presenting here are not representative
Stroke is classified into two major types:
Brain ischemia due to thrombosis, embolism, or systemic hypoperfusion
Brain hemorrhage due to intracerebral hemorrhage or subarachnoid hemorrhage
Approximately 80 percent of strokes are due to ischemic cerebral infarction and 20 percent to brain hemorrhage. Another cause of stroke is due to occlusion of veins that drain the brain of blood. Blood disorders are an uncommon primary cause of stroke. Increased blood coagulability can result in thrombus formation and subsequent cerebral embolism.
Atherosclerosis is by far the most common cause of in situ local disease. Vasoconstriction (eg, with migraine) is probably the next most common.
Delivery of adequate blood through a blocked or partially blocked artery depends upon many factors, including blood pressure, blood viscosity, and collateral flow.
Microatheromas can block small penetrating arteries called atheromatous branch disease).7
Embolic stroke symptoms depend upon the region of brain rendered ischemic.8 Treatment will depend upon the source and composition of the embolus.
Most studies evaluating secondary stroke risk have found that complex aortic atherosclerosis is a risk factor for recurrent stroke.9,10
In authors opinion, there is no question that large protruding plaques in the ascending aorta and arch, particularly mobile plaques, are an important cause of stroke.11
The most common causes of ICH are hypertension, trauma, bleeding diatheses, amyloid angiopathy, illicit drug use (mostly amphetamines and cocaine), and vascular malformations.12
Symptoms of SAH begin abruptly in contrast to the more gradual onset of ICH. Onset headache is more common than in ICH, and the combination of onset headache and vomiting is infrequent in ischemic stroke.13
Under normal conditions, the rate of cerebral blood flow is primarily determined by the amount of resistance within cerebral blood vessels, which is directly related to their diameter.14 Cerebral auto-regulation is the phenomenon by which cerebral blood flow is maintained at a relatively constant level despite moderate variations in perfusion pressure. The smooth muscle in cerebral vessels and the endothelial release of nitric oxide also appears to play a role in auto-regulation. Cerebral auto-regulation is impaired during some disease conditions, including ischemic stroke.14,15 In hypertensive individuals, auto-regulation has adapted to occur at higher arterial pressures.
Brain ischemia initiates a cascade of events that eventually lead to cell death, including depletion of ATP, changes in ionic concentrations of sodium, potassium, and calcium, increased lactate, acidosis, accumulation of oxygen free radicals, intracellular accumulation of water, and activation of proteolytic processes.16 Reactive oxygen species, can react with and damage cellular components. Inflammation results in the migration of activated leukocytes to damaged tissue which release cytokines to attract additional inflammatory cells. Under severe inflammatory conditions, these cytokines can accumulate to toxic levels.17
A 2012 meta-analysis of genome-wide association studies (GWAS) that analyzed data from over 12,000 subjects of European ancestry with ischemic stroke and 60,000 controls identified three loci (PITX2, ZFHX3, and HDAC9) with genome-wide significance for ischemic stroke.
Ethnic differences may also contribute to stroke risk. As an example, individuals of African descent have a significantly higher rate of stroke than Caucasians. In a study of 1398 individuals with sickle cell anemia, 12 genes were found to interact with the mutated hemoglobin and modulate the risk of stroke.18
Patients suffering a stroke may present with other serious medical conditions. Thus, the initial evaluation requires a rapid but broad assessment.19
Diagnosing an intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) as soon as possible can be lifesaving.19
Hyperglycemia blood glucose level >126 mg/dL (>7.0 mmol/L), is common in patients with acute stroke and is associated with poor functional outcome.20
A number of reports suggest that cerebral perfusion pressure or intracranial large artery flow velocity is maximal when patients are in the horizontal position.29Thus, a supine position is preferred for non-hypoxic patients with acute ischemic stroke who are able to tolerate lying flat.21
It is concluded that at current sample size, we accept the null hypothesis that there is no association between raised gamma-glutamyl transferase and ischemic stroke as the frequencies of raised gamma-glutamyl transferase were comparable among cases and controls. Odds ratio came out 1.44 ((at 95% CI, 0.992 to 2.103).