248 Int. J. Med. Med. Sci.
Table 1. Baseline characteristics of all patients (n=357).
Continuous variable Range Min-maximum
Age (years) 63 35-95
Categorical variable Frequency Percentage
Male 226 63.3
Female 131 36.7
Components of metabolic syndrome Male Female Male Female
Three 41/165 124/165 24.8 75.2
Systolic blood pressure >130 mmHG 65/165 100/165 39.39 60.60
Triglyceride levels >150 mg /dl 62/183 121/183 33.87 66.12
HDL levels < 50 mg/dl female and < 40 mg/dl in male 62/234 172/234 26.49 73.50
waist circumference >90 cm in male and >80 cm in female 123 34.45
FBS >100 mg/dl 126 35.29
FBS = fasting blood sugar; HDL= high density lipoprotein.
observe the frequency of metabolic syndrome and its’ HDL and LDL cholesterol levels. Glucose levels were measured by
various components in patients with ischemic stroke. enzymatic assay using an Eppendorf 5060 auto-analyzer.
Patients were diagnosed as metabolic syndrome on the basis of
ATPIII (Alberti, 2005) criteria which include presence of at least
MATERIALS AND METHODS three features: 1) blood pressure of at least 130/85 mmHg or trea-
ted hypertension, 2) serum triglyceride level of at least 150 mg/dl
This descriptive case study was conducted in Liaquat University (1.7 mmol/l), 3) HDL cholesterol of < 40 mg/dl (1.03 mmol/L) in men
Medical and Health Sciences hospital, Hyderabad, Pakistan from and < 50 mg/dl (1.29 mmol/L) in women, 4) fasting glucose of > 100
June, 2008 to November, 2009. This is a tertiary care hospital for mg/dl (5.6 mmol/l) or previously diagnosed with type 2 diabetes and
about 20 million urban, rural and multi-ethnic populations. The 5) central obesity, waist circumference greater than 90 cm in men
study included 357 consecutive patients of either sex presented and 80 cm in female according to Population- and country-specific
with ischemic stroke. The study was started after approval of the definitions (WHO Expert Consultation, 2004).
university ethical committee. Informed consent was taken from the
patients or their relatives. During the first visit, records were
obtained on the patient’s medical history. The conventional risk fac-
tors such as body weight, body mass index (BMI), blood pressure
measurement, history of smoking, a past history of stroke, family Continuous variables such as age was expressed as range with
history of stroke, use of antidiabetic, antihypertensive, and minimum and maximum. Categorical variables such as sex, pres-
antihyperlipidemic drugs were enrolled in well designed proforma. A ence or absence of metabolic syndrome, components of metabolic
complete physical examination was performed. Stroke was defined syndrome HDL levels > or < 50mg/dl in female and > or < 40 mg/dl
as a focal neurological disorder with rapid onset which persisted at in male, waist circumference > or < 90 cm in men and > or < 80 cm
least 24 h or until death and had a brain CT that showed a in women, triglyceride levels > or < 150 mg /dl, fasting glucose of >
compatible low-density lesion (Shimamoto et al., 1989). or < 100 mg/dl, blood pressure of at least 130/85 mmHg were
For each patient, blood pressure was taken after 15 min of rest. It expressed as percentage and frequency. The chi-square test was
was measured by a mercury sphygmomanometer with the subject applied to compare categorical variables such as metabolic syn-
seated comfortably with the arm supported and positioned at the drome, HDL levels, waist circumference, systolic blood pressure,
level of the heart. The final blood pressure estimate was the triglyceride levels and fasting blood sugar with the ischemic stroke.
average of three readings. Neither smoking nor caffeine was per- A p-value of 0.05 was considered as statistically significant. All
mitted before the blood pressure measurement. Individuals on calculations were done using SPSS version 16 (Chicago, IL, USA).
antihypertensive medications were considered as hypertension
patients regardless of blood pressure levels. Waist circumference
was measured by a trained examiner using a measuring tape RESULTS
positioned midway between the lowest rib and the iliac crest. All
study participants were individually interviewed by trained medical This study included 357 patients of which 131 (36.7%)
students with a structured questionnaire to obtain information on were male and 226 (63.3%) were female. The age of the
socio-demographic characteristics, physical activity and exercise patients ranged from 35 to 95 years. Table 1 shows the
habits (yes vs. no, deﬁned by less than 20 min exercise per week), baseline characteristics of patients. The three compo-
smoking, and alcohol consumption. For baseline examination,
nents of metabolic syndrome was present in 165 (46.2%)
blood was drawn from patients into a plain, siliconized glass tube
and the serum was separated. Fasting serum samples were stored patients of which 41/165(24.8%) were male and 124/165
at -7° prior to the batch assay using standard enzymatic tests for
C (75.2%) were female (0.001). Systolic blood pressure g
cholesterol and triglyceride levels and precipitation methods for was present in 165 patients of which 65 were male and
Shaikh et al. 249
Table 2. Comparision of various categorical variables with ischemic stroke.
Variable Frequency Percentage P value
Three components of metabolic syndrome 165 46.2 0.001*
Male 41 24.8
Female 124 75.2
HDL levels < 50mg/dl female and < 40 mg/dl in male 234 65.5 0.001*
Triglyceride levels >150 mg /dl 183 51.26 0.153
Systolic blood pressure >130mm Hg 165 46.21 0.001*
FBS > 100mg/dl 126 35.29 0.421
Waist circumference >90 cms in male and >80cms in female 123 34.45 0.001*
*P value < 0.05 is statistically significant . FBS = fasting blood sugar; HDL= high density lipoprotein.
100 were female (0.137). FBS > 100 mg/dl was present 23 times greater in female than male persons with
in 126 patients of which 57 had metabolic Syndrome metabolic syndrome. The Northern Manhattan study
(0.421).Triglyceride levels >150 mg/dl was present in183 which included Hispanic, African-American, and
cases of which 62 were male and 121 female (0.153). Caucasian subjects, reported an increased risk of stroke
Waist circumference greater than 90 cm in men and 80 among women with metabolic syndrome [hazard ratio
cm in female was present in 123 patients of which 90 had (HR=2.1)] compared to men (HR=0.9) (Rincon et al.,
other components of metabolic syndrome (0.001) HDL 2009). Koren and Morag (2005) similarly reported that
levels < 50mg/dl was present in172 female and >40 metabolic syndrome without diabetes mellitus was a
mg/dl in 62 male (0.001). Table 2 shows comparison of significant risk factor for ischemic stroke in both sexes,
different categorical variables with the ischemic stroke. but the effect was more pronounced in women [odds ratio
(OR=2. 10)] than in men (OR=1. 39). On the other hand,
Kurl et al. (2006) reported that the risk of ischemic stroke
DISCUSSION is significantly increased in men with metabolic syndrome
in Finland. The result of theirs might be due to the long
In this case study, metabolic syndrome was found in follow-up period (average follow-up of 14.3 years).
46.3% of patients, with ischemic stroke making a signifi- Dyslipidemia which is characterized by high
cant association. Our observation was supported by triglycerides and low HDL has always been considered
Gorter et al. (2004) who found metabolic syndrome in 40 as a hallmark of the MetSyn. Our data has shown strong
to 50% of patients with various cardiovascular diseases. association between dyslipidemia and ischemic stroke as
Metabolic syndrome was present in 56% of patients with triglyceride levels >150 mg /dl was present in183 cases
ischemic stroke in a study conducted by Koren and and HDL levels <50mg/dl was present in 172 female and
Morag (2005). De Silva (2007) recorded metabolic syn- >40 mg/dl in 62 male. According to Copenhagen City
drome in 61% of South Asian patients. In Third National Heart Study, a 47% reduction in ischemic stroke was
Health and Nutrition Examination survey of 15922 sub- found for 1.0 mmol/l (39 mg/dl) rise in HDL (Lindenstrom,
jects, metabolic syndrome was significantly associated 1994). Our study is also in consistence with Milionis et al.
with self reported stroke (odds ratio 2.2; 95% CI, 1.5 to (2005) which stated that high TG levels and low HDL-C
3.2) (National Institutes of Health , 2001). In Framingham levels had a relationship with ischemic stroke. The British
offspring study, metabolic syndrome was found more regional heart study, a prospective study consisting 7735
important risk factor for ischemic stroke as compared to men followed up for 16.8 years, also revealed a signifi-
diabetes mellitus (19 vs. 7%) (Najarian et al., 2006) .The cant association between HDL levels and stroke with a
Atherosclerosis Risk in Communities (ARIC) study also relative risk (RR) for nonfatal stroke was 0.59 (95% conﬁ-
noted that patients with metabolic syndrome have higher dence interval, CI, 50.39 to 0.90; P50.03) (Wannamethee
risk of incident stroke (hazard ratio, 2.74 to 4.16 com- et al., 2000).
pared to the reference group) provided the metabolic In the Finnmark study, a 51.29% increase in stroke in
syndrome contains either high blood pressure or elevated women was seen for each 1.0 mm/l (88.5 mg/dl) increase
fasting blood sugar (Sol et al., 2009). In our study, meta- in TG levels (Njolstad et al., 1996). The Framingham
bolic syndrome was found in 75.2% female as compared study (Gordon et al., 1981) contradicts these results by
to 24.8% male. Takahashi et al. (2007) in their study observing that HDL had a non-significant effect on the
noted that the chances of developing ischemic stroke are development of ischemic stroke in either sex. The
250 Int. J. Med. Med. Sci.
contradiction in results may be attributed to differences in Study: Stroke, 39:30-35.
De Silva DA, Fung PW, Xiao YX, Christopher LHC, Hui MC, Meng CW
sample size as in the Copenhagen study the number of (2007). Metabolic Syndrome Among Ethnic South Asian Patients
subjects studied were 11,342 vs. 2723 in the With Ischemic Stroke and Comparison With Ethnic Chinese Patients:
Framingham study. The Singapore General Hospital Experience: J. Stroke Cerebrovasc.
High blood pressure has emerged as an important Dis., 16(3): 119-121.
component in our patients as 165 patients had systolic Gorter PM, Olijhoek JK, van der GY (2004) Prevalence of the metabolic
syndrome in patients with coronary heart disease, cerebrovascular
blood pressure >130 mm of HG. In NOMAS study, a disease, peripheral arterial disease or abdominal aortic aneurysm.
linear relationship between blood pressure and risk of Atherosclerosis, 173: 363-369.
ischemic stroke and other vascular events such as fatal Gordon T, Kannel WB, Castelli WP, Dawber TR (1981) Lipoproteins,
cardiovascular disease and death: the Framingham study. Arch. Int.
or nonfatal hospitalized myocardial infarction, fatal CHD,
Med., 141: 1128-1131.
silent myocardial infarction was found with an increase in Howard BV. (1999). Insulin resistance and lipid metabolism. Am. J.
either event by 35% (Boden-Albala et al., 2008). McNeill Cardiol., 84: 28-32.
and Rosamond (2006) have found high blood pressure Isomma B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Groop L
(2001). Cardiovascular morbidity and mortality associated with the
as an important component of metabolic syndrome which metabolic syndrome. Diabetes Care, 24: 683-689.
increased the risk of ischemic stroke by 1.5 and 2 times Kazuo T, Hirokazu B, Shotai K, Kenichi I, Atsushi N, Shuhei Y (2007)
after adjustment for established risk factors. Metabolic Syndrome Increases the Risk of Ischemic Stroke in
Increased waist circumference which represents abdo- Women: internal medicine Tokyo Japan, 46(10): 643-648.
minal obesity has a strong association with stroke in our Kurl S, Laukkanen JA, Niskanen L (2006).Metabolic syndromeand the
risk of stroke in middle-aged men. Stroke, 37: 806-811
study as a waist circumference greater than 90 cm in Lindenstrom E, Boysen G, Nyboe J (1994) Inﬂuence of total cholesterol,
men and 80 cm in female was present in 123 patients. high-density lipoprotein cholesterol, and triglycerides on risk of
Isomma (2001) in study of 6,645 persons noticed obesity cerebrovascular disease: the Copenhagen City Heart Study. BMJ,
in 76% of men with normal glucose tolerance (NGT) and
Liu J, Grundy SM, Wang W, Smith SC Jr, Vega GL, Wu Z, Zeng Z,
92% of diabetic men with ischemic stroke.Helsinki Police- Wang W, Zhao D (2007) Ten-year risk of cardiovascular incidence
men Study has also shown a moderate association with related to diabetes, prediabetes, and the metabolic syndrome. Am.
HR (hazard ratios) 2.12 (1.28 to 3.49) between metabolic Heart J., 153: 552-558.
syndrome and stroke with special emphasis on obesity as Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ (2006)
Global and regional burden of disease and risk factors: systematic
a risk factor (Marja Pyörälä, 1998). Visceral fat which analysis of population health data. Lancet, 367: 1747–57.
constitutes abdominal obesity is postulated to release Marja P, Heikki M, Markku L, kalevi P (1998) Hyperinsulinemia and the
free fatty acids and increases the synthesis and secretion Risk of Stroke in Healthy Middle-Aged Men : The 22-Year Follow-Up
of very-low-density lipoproteins (VLDLs) (Tripathy et al., Results of the Helsinki Policemen Study Stroke, 29: 1860-1866.
McNeill A, Katz R, Girman C, Rosamond W, Wagenknecht L, Brazilay J,
2003). This increase release of FFA plays a pivotal role in Tracy R, Savage P, Jackson S (2006). Metabolic syndrome and
the pathogenesis of insulin resistance which is a hallmark cardiovascular disease in the elderly. The Cardiovascular
of metabolic syndrome (Howard et al., 1999). HealthStudy. J. Am. Geriatr. Soc., 54(9):1317-24.
Milionis HJ, Rizos E, Goudevenos J, Seferiadis K, Mikhailidis DP, Elisaf
There was a lack of association between glucose
MS (2005) Components of the metabolic syndrome and risk for
abnormality and the risk of stroke in our study. This could ﬁrstever acute ischemic nonembolic stroke in elderly subjects. Stroke
be due to inclusion of patients with mild to moderate 36:1372–6.
glucose abnormality in our study. Liu et al. (2007) has Koren-Morag N, Goldbourt U, Tanne D (2005) Relation between the
also shown in their study that glucose abnormality can Metabolic Syndrome and Ischemic Stroke or Transient Ischemic
AttackA Prospective Cohort Study in Patients with Atherosclerotic
only increase the risk of ischemic stroke by 14%. This Cardiovascular Disease. Stroke, 36: 1366-1371.
study has its limitations. The results of this study cannot National Institutes of Health (2001). Third Report of the National
be generalized to the population as this is not a case Cholesterol Education Program Expert Panel on Detection,
Evaluation and Treatment of High Blood Cholesterol in Adults (Adult
control study which requires the prevalence of metabolic
Treatment Panel III). Washington DC: US Government Printing
syndrome in the normal population in Pakistan. Office. NIH Publication No. 01-3670.
Metabolic syndrome is a frequent occurrence in Najarian RM, Lisa MS, William BK, Peter WFW, Ralph BDA, Philip AW
patients with ischemic stroke. It is not only metabolic syn- (2006). Metabolic Syndrome Compared With Type 2Diabetes Mellitus
as a Risk Factor for Stroke; The Framingham Offspring Study. Arch.
drome, but its individual components have emerged as
Int. Med., 166: 106-111
an important risk factor for ischemic stroke. Its early Ninomiya J, L’Italian G, Criqui M, Whyte J (2004) Association of the
diagnosis and treatment of patients at risk may avert the metabolic syndrome with a history of myocardial infarction and stroke
development of ischemic stroke. Caring physicians in the third National Health and Nutrition Examination Survey.
should look for metabolic syndrome and expect it in about Circulation, 109: 42–46.
Njolstad I, Arnesen E, Lund-Larsen PG (1996) Body height,
half of their patients. More studies are warranted. cardiovascular risk factors and risk of stroke in middle-aged men and
women. Circulation, 94: 2877–2882.
Park JH, Kwon HM, Roh JK (2007) Metabolic syndrome is more
REFERENCES associated with intracranial atherosclerosis than extracranial
atherosclerosis. Eur. J. Neurol., 4: 379-386.
Alberti KG, Zimmet P, Shaw J (2005) The metabolic syndrome— a new Reaven G, Banting L (1988). Role of insulin resistance in human
worldwide deﬁnition. Lancet, 366: 1059-1062. disease. Diabetes, 37: 1595-1607.
Boden-Albala B, Ralph LS, Hye-Sueng L, Cairistine GC, Tanja R (2008) Rincon F, Ralph LS, Grace K, Qiu X, Myungee C (2009). Incidence
Metabolic Syndrome and Ischemic Stroke Risk: Northern Manhattan and Risk Factors of Intracranial Atherosclerotic Stroke: The Northern
Shaikh et al. 251
Manhattan Stroke Study. Cerebrovasc. Dis., 28: 65-71 and impairs vascular reactivity in healthy subjects. Diabetes, 52: 2882–
Shimamoto T, Komachi Y, Inada H, Doi M, Iso H, Sato S (1989) Trends 2887.
for coronary heart disease and stroke and their risk factors in Japan. Wannamethee SG, Shaper G, Ebrahim S (2000). HDL-Cholesterol, total
Circulation, 79: 503–515. Cholesterol and the risk of stroke in middle-aged British men. Stroke,
Sol M, Rodriguez-Colon MS, Jingping M, Yinkang D, Jiahao L, Joanne 31: 1882–1892.
EC, Xuejuan J, Duanping L (2009) Metabolic Syndrome Clusters and WHO (2008). Burden of Disease Statistics. Geneva, Switzerland: World
the Risk of Incident Stroke The Atherosclerosis Risk in Communities Health Organization. http://www.who.int/healthin-fo/bod/en/index.
(ARIC) Study. Stroke, 40: 200-205. Html.
Strong K, Mathers C, Bonita R. (2007) Preventing stroke: saving lives WHO Expert Consultation (2004). Appropriate body-mass index for
around the world. Lancet Neurol., 6: 182-187. Asian populations and its implications for policy and intervention
Syed NA, Khealani BA, Ali S, Hasan A, Akhtar N, Brohi H (2003) strategies [published correction appears in Lancet. 2004; 363: 902].
Ischemic stroke subtypes in Pakistan: the Aga Khan University Lancet, 363: 157-163.
Stroke Data Bank. J. Pak. Med. Assoc., 53: 584-88.
Tripathy D, Mohanty P, Dhindsa S, Syed T, Ghanim H, Aljada A,
Dandona P (2003) Elevation of free fatty acids induces inﬂammation