HOMOCYSTEINE AS
A RISK FACTOR OF
STROKE
DR SUDHIR KUMAR MD DM (Neurology)
Neurologist, Apollo Hospitals, Hyderabad
AIMS & OBJECTIVES
• To study the risk factors of stroke, with a special
emphasis on the role of homocysteine,
• To study the effect of homocysteine in : 1.
Ischemic vs hemorrhagic strokes, 2. Men vs
women stroke patients, 3. Younger vs older stroke
patients
PATIENTS & METHODS
• Setting: Apollo hospitals, Jubilee Hills, a JCI-
accredited stroke center,
• Patients admitted with stroke (ischemic or
hemorrhagic), presenting within 24 hours of
symptom onset were included,
• Risk factors for stroke were assessed, within 24
hours of admission,
• Duration of study: April 2013 to March 2015
RESULTS (1)
• Total number of patients- 451
• Mean age: Ischemic stroke (57.5 years),
hemorrhagic stroke (58.1 years)
• Stroke type: Ischemic (330; 73%), Hemorrhagic
(121; 27%)
• Gender: Male Female
Ischemic 236 (71.5% 94 (28.5%)
Hemorrhagic 87 (71.9%) 34 (28.1%)
RESULTS (2)
Risk
factor
Ischemic
(no.)
Ischemic
(%)
H’gic
(no.)
H’gic (%) P value
HT 207 63% 86 71% 0.079
DM 121 37% 38 31% 0.326
Smoking 71 21% 18 15% 0.116
Alcohol 72 22% 27 22% 0.91
Homocysteine 102 31% 40 33% 0.663
Low HDL 258 78% 88 73% 0.294
High LDL 160 49% 35 29% 0.001*
High TG 88 27% 19 16% 0.013*
High Chol 90 27% 22 18% 0.111
RESULTS (3)
Mean homocysteine concentration
Ischemic stroke (n=330): 13.77
Hemorrhagic stroke (n=121): 14.98
Overall (n=451): 14.09
P=0.527
RESULTS (4)
Distribution of patients with elevated homocysteine
in stroke risk categories:
1. Gender
Male: 118/323
Female: 22/128 p: 0.000*
RESULTS (5)
Age groups and elevated homocysteine
Age Patients High Hcy
(n)
High Hcy (%)
<44 years 67 33 49%
44-58 years 148 52 35%
58-72 years 169 47 28%
>72 years 67 10 15%
P=0.000*
Younger patients with stroke had significantly higher homocysteine
RESULTS (6)
1. Hypertension
Yes: 95/293; No: 47/158 p=0.588
2. Diabetes
Yes: 41/159; No: 100/292 p=0.061
3. Smoking
Yes: 32/89; No: 110/362 p=0.311
4. Alcohol
Yes: 40/99; No: 102/352 p=0.031*
RESULTS (7)
Significant association of elevated Homocysteine with LDL and total cholesterol
1. HDL
<40: 110/333; >40: 37/118 p=0.972
2. LDL
<100: 61/256; >100: 81/195 p=0.001*
3. TG
<150: 100/340; >150: 46/111 p=0.057
4. Total Cholesterol
<200: 90/340; >200: 47/111 p=0.029*
RESULTS (8)
Mean serum values of homocysteine
Males: 15.81; Females: 10.17 p=0.003*
<44 years: 20.94
44-58 years: 13.96
58-72 years: 13.22
>72 years: 9.7 p=0.003*
Homocysteine values did not differ between those with or
without DM, HTN, Smoking or alcohol.
DISCUSSION (1)
• Elevated homocysteine level is an independent risk
factor of stroke. (Lancet 1995)
• Mechanisms: endothelial cell damage, smooth muscle cell proliferation, lipid
peroxidation, upregulation of prothrombotic factors, downregulation of
antithormbotic factors
• About 30% of patients with stroke have elevated
homocysteine levels.
• Elevated homocysteine as a risk factor for stroke is
more common in males, younger patients, those
actively drinking, pure vegetarians, and in those with
high LDL/total cholesterol.
DISCUSSION (2)
• Meta-analysis of nine studies with >13,000
patients (NMCD 2014)
• Correlation between homocysteine levels and
stroke was studied.
• Significant association with elevated
homocysteine levels and ischemic/recurrent
stroke
• No association with hemorrhagic stroke.
DISCUSSION (3)
• Patients with hyperhomocysteinemia have lesions
typical of cerebral microangiopathy and tend to have
multiple infarctions. (Arch Neurol 1997)
• In an MRA brain based study, patients with 2- or 3-
vessel stenosis were found to have higher
homocysteine levels than those with 1-vessel stenosis.
(Stroke 1998)
• Stroke risk increases in proportion to the increase in
homocysteine levels.
• High homocysteine levels at admission can be a useful
test to pick up patients who are actively drinking.
(Alcohol Alcohol 2004)
DISCUSSION (4)
• High homocysteine levels in acute phase of
ischemic stroke (measured within 24 hours) can
predict mortality. (Stroke 2015)
• Patients with Hcy>18.6 had 1.6 times higher
mortality, as compared to those with Hcy<10.
• This correlation was significant only in large-artery
atherosclerosis; and not significant in small vessel
ischemic disease.
DISCUSSION (5)
• Long term daily treatment with vitamins (folic acid 2.5
mg, pyridoxine 50 mg and vitamin B12 1 mg) reduces
homocysteine levels (HOPE 2 study, Stroke 2009)
• Vitamin therapy reduced the risk of incident stroke, as
well as nonfatal stroke.
• Lowering homocysteine, however, had no effect on
stroke severity (at 24 hours) and disability (at 90 days)
• Optimal level of homocysteine is 10-12; those with >15
are considered to have elevated homocysteine.
CONCLUSIONS
• Elevated homocysteine is an important, strong, graded
and modifiable risk factor for ischemic and recurrent
strokes.
• Elevated homocysteine at baseline also predicts
higher long term mortality.
• Association is stronger in males, younger patients,
those with elevated LDL/cholesterol; vitamin B12
deficiency and regular alcohol consumers.
• Vitamin supplementation reduces the recurrence of
stroke.
QUERIES/COMMENTS
Contact
M: 9866193953
Email: drsudhirkumar@yahoo.com

Homocysteine as a risk factor in stroke

  • 1.
    HOMOCYSTEINE AS A RISKFACTOR OF STROKE DR SUDHIR KUMAR MD DM (Neurology) Neurologist, Apollo Hospitals, Hyderabad
  • 2.
    AIMS & OBJECTIVES •To study the risk factors of stroke, with a special emphasis on the role of homocysteine, • To study the effect of homocysteine in : 1. Ischemic vs hemorrhagic strokes, 2. Men vs women stroke patients, 3. Younger vs older stroke patients
  • 3.
    PATIENTS & METHODS •Setting: Apollo hospitals, Jubilee Hills, a JCI- accredited stroke center, • Patients admitted with stroke (ischemic or hemorrhagic), presenting within 24 hours of symptom onset were included, • Risk factors for stroke were assessed, within 24 hours of admission, • Duration of study: April 2013 to March 2015
  • 4.
    RESULTS (1) • Totalnumber of patients- 451 • Mean age: Ischemic stroke (57.5 years), hemorrhagic stroke (58.1 years) • Stroke type: Ischemic (330; 73%), Hemorrhagic (121; 27%) • Gender: Male Female Ischemic 236 (71.5% 94 (28.5%) Hemorrhagic 87 (71.9%) 34 (28.1%)
  • 5.
    RESULTS (2) Risk factor Ischemic (no.) Ischemic (%) H’gic (no.) H’gic (%)P value HT 207 63% 86 71% 0.079 DM 121 37% 38 31% 0.326 Smoking 71 21% 18 15% 0.116 Alcohol 72 22% 27 22% 0.91 Homocysteine 102 31% 40 33% 0.663 Low HDL 258 78% 88 73% 0.294 High LDL 160 49% 35 29% 0.001* High TG 88 27% 19 16% 0.013* High Chol 90 27% 22 18% 0.111
  • 6.
    RESULTS (3) Mean homocysteineconcentration Ischemic stroke (n=330): 13.77 Hemorrhagic stroke (n=121): 14.98 Overall (n=451): 14.09 P=0.527
  • 7.
    RESULTS (4) Distribution ofpatients with elevated homocysteine in stroke risk categories: 1. Gender Male: 118/323 Female: 22/128 p: 0.000*
  • 8.
    RESULTS (5) Age groupsand elevated homocysteine Age Patients High Hcy (n) High Hcy (%) <44 years 67 33 49% 44-58 years 148 52 35% 58-72 years 169 47 28% >72 years 67 10 15% P=0.000* Younger patients with stroke had significantly higher homocysteine
  • 9.
    RESULTS (6) 1. Hypertension Yes:95/293; No: 47/158 p=0.588 2. Diabetes Yes: 41/159; No: 100/292 p=0.061 3. Smoking Yes: 32/89; No: 110/362 p=0.311 4. Alcohol Yes: 40/99; No: 102/352 p=0.031*
  • 11.
    RESULTS (7) Significant associationof elevated Homocysteine with LDL and total cholesterol 1. HDL <40: 110/333; >40: 37/118 p=0.972 2. LDL <100: 61/256; >100: 81/195 p=0.001* 3. TG <150: 100/340; >150: 46/111 p=0.057 4. Total Cholesterol <200: 90/340; >200: 47/111 p=0.029*
  • 12.
    RESULTS (8) Mean serumvalues of homocysteine Males: 15.81; Females: 10.17 p=0.003* <44 years: 20.94 44-58 years: 13.96 58-72 years: 13.22 >72 years: 9.7 p=0.003* Homocysteine values did not differ between those with or without DM, HTN, Smoking or alcohol.
  • 13.
    DISCUSSION (1) • Elevatedhomocysteine level is an independent risk factor of stroke. (Lancet 1995) • Mechanisms: endothelial cell damage, smooth muscle cell proliferation, lipid peroxidation, upregulation of prothrombotic factors, downregulation of antithormbotic factors • About 30% of patients with stroke have elevated homocysteine levels. • Elevated homocysteine as a risk factor for stroke is more common in males, younger patients, those actively drinking, pure vegetarians, and in those with high LDL/total cholesterol.
  • 14.
    DISCUSSION (2) • Meta-analysisof nine studies with >13,000 patients (NMCD 2014) • Correlation between homocysteine levels and stroke was studied. • Significant association with elevated homocysteine levels and ischemic/recurrent stroke • No association with hemorrhagic stroke.
  • 15.
    DISCUSSION (3) • Patientswith hyperhomocysteinemia have lesions typical of cerebral microangiopathy and tend to have multiple infarctions. (Arch Neurol 1997) • In an MRA brain based study, patients with 2- or 3- vessel stenosis were found to have higher homocysteine levels than those with 1-vessel stenosis. (Stroke 1998) • Stroke risk increases in proportion to the increase in homocysteine levels. • High homocysteine levels at admission can be a useful test to pick up patients who are actively drinking. (Alcohol Alcohol 2004)
  • 16.
    DISCUSSION (4) • Highhomocysteine levels in acute phase of ischemic stroke (measured within 24 hours) can predict mortality. (Stroke 2015) • Patients with Hcy>18.6 had 1.6 times higher mortality, as compared to those with Hcy<10. • This correlation was significant only in large-artery atherosclerosis; and not significant in small vessel ischemic disease.
  • 17.
    DISCUSSION (5) • Longterm daily treatment with vitamins (folic acid 2.5 mg, pyridoxine 50 mg and vitamin B12 1 mg) reduces homocysteine levels (HOPE 2 study, Stroke 2009) • Vitamin therapy reduced the risk of incident stroke, as well as nonfatal stroke. • Lowering homocysteine, however, had no effect on stroke severity (at 24 hours) and disability (at 90 days) • Optimal level of homocysteine is 10-12; those with >15 are considered to have elevated homocysteine.
  • 18.
    CONCLUSIONS • Elevated homocysteineis an important, strong, graded and modifiable risk factor for ischemic and recurrent strokes. • Elevated homocysteine at baseline also predicts higher long term mortality. • Association is stronger in males, younger patients, those with elevated LDL/cholesterol; vitamin B12 deficiency and regular alcohol consumers. • Vitamin supplementation reduces the recurrence of stroke.
  • 19.