PCV (%) -0.118 0.154
Total Cholesterol (mg/dl) -0.077 0.352
HDL Cholesterol (mg/dl) -0.306 <0.001
LDL Cholesterol (mg/dl) -0.116 0.161
Triglyceride (mg/dl) 0.153 0.065
Urea (mg/dl) -0.015 0.857
Creatinine (mg/dl) 0.094 0.257
LDL=low density lipoprotein, HDL= high density lipoprotein, FBS= Fasting blood sugar, PCV= packed cell volume
Table 8a: Comparison of the biochemical and Hamatological characteristics between Stroke types
IS (N=92) HS (N=56)
Mean SD Mean SD t p
Homocysteine Level 8.05 4.79 6.58 2.18 2.541 0.012 FBS (mg/dl) 141.0 59.5 148.9 51.4 -0.855 0.394
PCV (%) 38.6 4.7 39.1 4.8 -0.611 0.542
Total Cholesterol (mg/dl) 199.9 71.2 169.6 61.5 2.719 0.007 HDL Cholesterol (mg/dl) 47.2 16.9 58.9 16.0 -4.215 <0.001 LDL Cholesterol (mg/dl) 119.2 42.2 108.7 35.7 1.617 0.108 Triglyceride (mg/dl) 148.9 78.1 117.3 46.7 3.076 0.003 Urea (mg/dl) 38.2 25.0 38.5 23.8 -0.092 0.927 Creatinine (mg/dl) 0.93 0.28 0.94 0.34 -0.111 0.912
IS =Ischemic stroke, HS = Hemorrhagic stroke, SD = Standard deviation, LDL=low density lipoprotein, HDL= high density lipoprotein, FBS= Fasting blood sugar, PCV= packed cell volume.
STROKE SUBTYPES
Table 8b Frequency of hyperhomocysteine levels in stroke subtype
Homocysteine IS n=92 HS n=56 Total
Elevated (>16.5) 10(10.9%) 0(0%) 10(6.8%)
Total 92(100%) 56(100%) 148(10%)
IS =Ischemic stroke, HS= Hemorrhagic stroke. Fisher’s exact test (p=0.025) Stroke Type
4.8: COMPARISON OF THE CLINICAL AND BIOCHEMICAL
CHARACTERISTICS OF STROKE CASES WITH HIGH AND NORMAL HOMOCYSTEINE LEVELS.
Table 9a shows that there a significant difference in diastolic blood pressure (t = 2.931; p = 0.004), GCS at presentation (t = 2.918; p = 0.004) and mRS at six weeks (t= -3.791; p < 0.001) between stroke cases with high and normal homocysteine levels. On the other hand, table 9b shows that there was a significant difference in the homocysteine level (t = -16.962; p <0.001), HDL cholesterol (t = 4.518, p <0.001) and triglycerides (-3.819; p < 001) between stroke cases with high and normal homocysteine levels.
Table 9a: Comparison of the clinical characteristics of stroke cases with high and normal homocysteine levels at presentation.
HOMOCYSTEINE LEVEL
LOW N = 138
HIGH
N= 10
Mean SD Mean SD t P Pulse Rate 88.0 14.8 96.8 15.0 -1.826 0.070 Blood Pressure Systolic 169.6 34.4 149.4 31.3 1.801 0.074 Blood Pressure Diastolic 98.4 19.3 80.1 16.5 2.931 0.004 GCS at presentation 11.2 3.7 7.6 4.2 2.918 0.004 CNS at Presentation 4.8 2.4 4.0 2.8 1.018 0.282 MRS at 6weeks 3.70 1.8 5.9 0.3 -3.741 <0.001
GCS=Glasgow Coma Score, CNS= Canadian Neurological scale
Table 9b: Comparison of the biochemical parameters between stroke cases with high and normal homocysteine levels of the cases at presentation
FBS = Fasting blood sugar, PCV = Packed cell volume, HDL =High density lipoprotein
Mean SD Mean SD t P
FBS 144.3 57.2 139.2 48.5 0.276 0.783
PCV 38.9 4.6 36.2 6.4 1.789 0.076
Total Cholesterol 188.1 68.5 195.1 80.1 -0.309 0.758
HDL_C 53.2 16.5 28.9 15.0 4.518 <0.001
LDL_C 115.4 39.7 113.3 47.4 0.159 0.874
Triglyceride 131.4 61.8 214.7 116.8 -3.819 <0.001
Homocysteine level ( µmol/l )
NORMAL n=138
<16.5
HIGH n=10
>16.5
CHAPTER FIVE DISCUSSION
Increased serum homocysteine has been identified as an independent risk factor for atherosclerosis, coronary heart disease and peripheral vascular disease.11,12 This risk is proposed to induce the modification of endothelial function which may involve cytotoxic and oxidative stress mechanisms. The frequency, pattern and correlates of homocysteine levels were studied in patients who had acute stroke for the very first time.
In this study, majority (85.1%) of the patients were in their 6th decade of life or older. Age is regarded as the single most important risk factor for stroke.155 For each successive 10 years after age 55, the stroke rate more than doubles in both men and women.146 The male patients (50.7%) were slightly more than the female patients (49.3%). This agrees with most studies
which suggests a male preponderance in the development of acute stroke.25,153,155
Majority (91.9%) of the stroke patients were Christians this could be explained by the fact that Christianity is the predominant religion in the setting of the study. This was also reflected in the control group. Only a minority (14.2.%) of the stroke patients had no formal education with most having attained at least a primary level of education. The main occupation were farming, petty business and retired public servants. This may be because of the age distribution of the patients and the setting of the study, where there is huge informal sector based economy.
Most (62.2%) of the stroke patients were known hypertensive and most of these patients were on treatment. There were more stroke patients with hypertension than the control group, they were however less adherent with their medication compared to the control group. This may partly explain why they (controls) were less morbid compared to the stroke subjects.
Hypertension is the single most important modifiable risk factor for ischemic stroke.166-167 Estimates for hypertension indicate a relative risk of stroke of approximately 4 when hypertension is defined as systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure
≥95 mm Hg.167-168 From population surveys the prevalence of hypertension is about 20% at age 50, about 30% at age 60, 40% at age 70, 55% at age 80, and 60% at age 90.158-169
Although not statistically significant, the diabetic stroke patients (22.1%) were more compared to the controls (17.3%). Diabetes is regarded as a risk factor for stroke and this probably explains the higher percentage of diabetics in the study group compared to the control. Diabetics have an increased susceptibility to atherosclerosis and an increased prevalence of atherogenic risk factors, notably hypertension, obesity, and abnormal blood lipids.169 Among Hawaiian Japanese men in the Honolulu Heart Program, those with diabetes had twice the risk of thromboembolic stroke of persons without diabetes that was independent of other risk factors.170There were slightly more stroke cases who had a history of smoking and alcohol intake than the control group. Smoking and excessive alcohol intake
are considered as important risk factors for strokes.93-96
There were more ischemic strokes (62.2%) than hemorrhagic strokes (37.8%). This agrees with other similar studies.12,44 Notably, about half of the cases had severe stroke by CNS.
This is higher than that seen in a previous Nigerian study.25
Stroke outcome at 6 weeks was assessed using Modified Rankin Score (mRS). It was found that majority (77%) of the stroke cases had poor outcome i.e. mRS above 2(still on admission, and considered not fit to be discharged) with a 31.5% case fatality. while the rest of the stroke survivors had good recovery mRS<2 and were already discharged.
The study found that only 6.8% of the stroke cases had hyper homocysteinemia (defined by the mean + 2 SD of controls) which was similar (6%) to the control group with no statistical difference between the two groups.This was slightly lower than an earlier study that found
10.1% and 12.2% for cases and control respectively.25 This was however in contrast to the study done in Accra, Ghana which found a much higher frequency of stroke patients with hyperhomocysteinemia (95%) as well as the control group (25%).153 Two previous studies conducted by Glew et al, in the North-eastern region of Nigeria (Maiduguri and Gombe) showed that people living in that region tend to have a higher prevalence, in which about 85% of the stroke patients had hyperhomocysteinemia which was partly attributed to their staple dietary intake (cereals) that is low in folic acid and vitamin B12.16, 159
Previous studies on the level of homocysteinemia, most of which have been in Caucasians with a few exceptions, have been conflicting.153 In a study done by Lingren et al, where they compared plasma homocysteine levels in the acute and convalescent periods following stroke, they found that, in contrast to several earlier studies, the concentration of plasma homocysteine did not differ between cases and controls in the acute phase, and plasma homocysteine levels were in fact higher in the convalescent period following stroke. 12,19,160 This observation was also noticed by Happaniemi et al where they concluded that decreased homocysteine levels found on admission for acute ischemic stroke may reflect the strength of the acute-phase response rather than a pathogenetic event.160
This study however showed a significant difference in the levels of homocysteine between the two types of stroke i.e. ischemic and hemorrhagic strokes, with higher levels of homocysteine found in Ischemic strokes than Hemorrhagic strokes and all the stroke cases with elevated homocysteine levels were in fact ischemic. The finding was in contrast to a study done by Li et al, were they found no difference in the levels of homocysteine between ischemic and hemorrhagic strokes.12 The findings of a higher homocysteine level in ischemic strokes was found in a study by Boysen et al where a significant difference between ischemic and hemorrhagic stroke with the levels being higher in former was found. This, they attributed to
the vascular difference between both types and not just a reaction to an acute illness.161 This can beexplained from the current thinking of how homocysteine causes plaques in the arteries. It theorizes that a buildup of homocysteine in the body leads to overproduction of a highly reactive form of homocysteine that causes LDL to become aggregated,143 This reactive form, homocysteine thiolactone, is made from methionine in the liver by an enzyme that participates in protein formation and by other less well understood processes. The LDL-homocysteine thiolactone aggregates are released into the blood from the liver. These aggregates are then taken up by macrophages of the arterial wall, many of which are derived from wandering monocytes of the blood, to form foam cells of early arteriosclerotic plaques. These foam cells degrade LDL-homocysteine thiolactone aggregates and release fat and cholesterol into the developing plaques. The foam cells also release homocysteine thiolactone into surrounding cells of the arterial wall, affecting the way cells handle oxygen. As a result, highly reactive oxygen radicals accumulate within cells damaging the lining cells of the arteries, promoting blood clot formation and stimulating growth of arterial muscle cells which form fibrous tissue, mucoid matrix and degenerative elastic
tissue.145
This study did not find a significant correlation between homocysteine levels and the severity of the stroke cases. This lack of correlation between elevated plasma homocysteine on admission and stroke severity was also reported by Perini et al.151
The study however showed that plasma levels of homocysteine significantly correlated with the short-term outcome (measured by the Modified Rankin score at six weeks) following acute stroke. The apparent discrepancy between the relationship of homocysteine and stroke severity at presentation and its relationship with stroke outcome at six weeks suggest that stroke outcome is influenced by other factors other than stroke severity.
The age and severity of the stroke at presentation (using GCS and CNS score) correlated significantly with short-term outcome at six weeks.This study also showed that hyperhomocysteinemia (homocysteine levels above 16.5micromoles/l) predicted poorer stroke outcome, with a ninety(90%) percent fatality.The relationship between elevated homocysteine and stroke outcome from earlier studies has remained controversial, with some
studies finding an association while others have not.25,163-164,173 Mild hyperhomocysteinaemia is considered an inflammatory marker and an independent risk factor for atherosclerosis and atherothrombosis in the coronary, cerebral and peripheral vascular structures.17,161,162 It is therefore possible that the short term outcome might be a reflection of the extent of inflammation that occurred at the onset of an acute stroke.
This study did not find a significant correlation between homocysteine levels and the blood sugar at presentation. This is in tandem with other previous studies suggesting that there is no significant relationship between blood sugar and homocysteine.19,25,153 There was also no significant correlation between elevated homocysteine levels, urea and creatinine as against other previous studies that showed consistently that homocysteine levels increase with
increasing levels of creatinine.144,151,153The exclusion of cases with renal impairment from this study may explain this finding. There was a significant negative correlation between homocysteine levels and high density lipo-protein (HDL), suggesting that HDL decreases with increasing homocysteine levels as shown in some earlier studies.154,160, 165