Pierre Amarenco

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Metabolic Syndrome and Stroke Risk
GROUPE HOSPITALIER BICHAT-CLAUDE BERNARD
UNIVERSITÉ DENIS DIDEROT - PARIS 7

• Pierre Amarenco
• Professor and chairman
• Department of Neurology and Stroke centre
• Bichat Hospital
• Paris

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Stroke prevention where are we?

• Stroke incidence is increasing because of aging
  of population
• 1 million each year in western Europe
• Stroke mortality is decreasing
• Blood pressure control
• Cholesterol lowering
• Antithrombotic agents
• Smonking is decreasing
• But weight gain is an increasing epidemy

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Vascular Trends in Stroke MortalityFrance
Men
Women
Age-adjusted stroke death -60.9 men -60.4
women Age-adjusted all VD -42.9 -46.5
1979 stroke 30.1 of VD vs 2001 21.3 of VD
Corelation BPLA, CLA, smoking cessation Increase
health expanditure, PIB/inhabitant
Lavallée P, Labreuche J, Spieler JF, Jougla E,
Amarenco P.
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Modifiable Risk Factors and Relative Risk of
Stroke
Mainly atrial fibrillation. Sacco et al.
Stroke. 1997281507-1517.
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Observational Studies Association of Serum
Cholesterol and Stroke Rates
Prospective StudiesCollaboration
1.2
1.0
Adjusted Stroke Rate

• 45 prospectiveobservational cohorts
• Total of 450,000 individuals
• Mean follow-up of 16 yrs
• 13,397 strokes recorded

0.8
4.5
5.0
5.5
6.0
6.5
mmol/L
175
200
225
250
mg/dL
Total Cholesterol
Adjusted for study, age, sex, DBP, CAD hx, and
ethnicity.
Adapted from Prospective Studies Collaboration.
Lancet. 19953461647-1653.
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Overweight an increasing epidemy in France
Prevalence of overweight and obesity (IMC ? 25)
in young men (17 to 25 y-o)
1987
1996
G CAR 04 06 653
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Prevalence of Metabolic Syndrome in FranceDESIR,
n4293 (1994-96/1999)

• Prospective study in France
• 16 of men and 11 of women
• Most frequent component is high blood pressure,
  then lipid abnormalities
• Most stable component is waist circumference
• ? Still exists in 80 of cases after 3 years

G CAR 04 06 653
NCEP-ATP III definition
Balkau B et coll. Diabetes Metab. 2003
Nov29(5)526-32.
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Metabolic Syndrome and Stroke

• Abdominal obesity
• Men gt102 cm
• Women gt88 cm
• Hypertiglyceridemia 150 mg/dL
• Low HDL cholesterol
• Men lt40 mg/dL
• Women lt50 mg/dL
• High blood pressure 130/85
• High fasting glucose gt100mg/dL

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Age-Adjusted Rates of Stroke per 1000 P-Y in 7649
British men
7.3
6.4
6.0
2.7
n7093
n138
n98
n320
1.00
2.21 (1.27-3.86)
2.30 (1.62-3.28)
2.81 (1.54-5.13)
RR
Wannamethee et al. Stroke 1999301780
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Intensive Blood Glucose Control Prevents
Microvascular and not Macrovascular Complications
UKPDS-33. Lancet 1998352837-53
MICROVASCULAR . Retinopathy requiring
photocoagulation . Vitreous hemorrhage . Fatal
and nonfatal renal failure

17.4
14.7
11.5
11.4
10.4
8.6
5.6
5.0
-25 -40 to -7
P0.0099
P0.052
P0.34
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Relation between stroke risk and SBP Difference
Staessen et al. 2001
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UKPDS 38
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PROGRESS
Stroke by medical historyAll participants
Favours placebo
Favours active
Hazard ratio (95CI)
Events active placebo
Hypertensive 163 235 Not
hypertensive 144 185 Diabetes
48 65 No diabetes 259
355 Ischaemic 236 307
Haemorrhagic 28 49 TIA
amaurosis 33 49 Total
307 420
0.67 (0.55-0.81) 0.78 (0.63-0.97) 0.67
(0.46-0.98) 0.72 (0.62-0.85) 0.76
(0.64-0.90) 0.52 (0.33-0.83) 0.66
(0.42-1.02) 0.72 (0.62-0.83)
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Bezafibrate Infarction Prevention (BIP) Study
Tanne D et al. Circulation 2001
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VA-HIT Stroke End-Point
Gemfibrozil - Fibric acid agent (PPAR agonist)
F-U 5.1 yr HDL 6 higher LDL 4 lower TG 31 lower
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VA-HIT(Veterans Administration-HDL Intervention
Trial)
F-U 5.1 yrs Gembibrozil 1200 mg/d Age lt74 yrs,
documented CHD
LDL lt140 mg/dl in 40 of CHD Low LDL HDL in 25
HDL 40 mg/dl LDL 140 mg/dl TG 300 mg/dl Men
Nonfatal MI CHD death (Primary outcome
event) MI Stroke TIA Endarterectomy Total
Death
Placebo N 1267 274 (21.6) 88 (6.9) 76
(6) 53 (4.2) 3.5 219 (17.3)
Risk Reduction 22 7-35 26 23 59.5 65 9.
8
P value 0.006 0.05 0.098 0.001 0.001 ns
Gemfibrozil N 1264 219 (17.32) 64 (5.1) 58
(4.6) 22 (1.7) 1.3 197 (15.6)
Bloomfield Rubins et al. New Engl J Med
1999341410-418
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Stroke mortality and the apoB/apoA1 ratio The
AMORIS study in 175 553 swedesh (98 722 men, 76
831 women, mean follow-up 10.3 years)
All strokes (n 1111)
Walldius et al. J Intern Med 2006 259 259-266
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British Regional Heart Study
7,735 men 40-59 y-o F/U 16,8 yrs 343 incident
strokes
OR
1
1
1.02
1
0.8
Trend p 0.03
0.68
Adjusted age, BMI, SBP, smoking, physical
activity,, alcohol intake, diabetes, pre-existing
CHD, Antihypertensive treatment
0
5th
1st
4th
3rd
2nd
quintile
HDL
lt 0.93
1.33 mmol/L
1.06-1.17
0.93-1.05
1.18-1.32

• Strong, independent risk factor for stroke

Wannamethee et al. Stroke 2000
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Relative risk estimates for stroke associated
with high HDL-C levels in several epidemiologic
studies
Amarenco P, Labreuche J, Touboul P-J. In
preparation
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Fibrinogen - MI - StrokeMeta-analysis of 154,211
subjects
JAMA Oct 2005
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Fibrinogen - MI - StrokeMeta-analysis of 154,211
subjects
JAMA Oct 2005
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Interaction CRP - TCHDL-C
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NHANES MI-Stroke and Met Synd
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WASID intracranial stenosis and Met Synd
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Carotid Stenosis
Carotid Plaque
Carotid Intima-Media Thickness (IMT)
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Between-Group LDL Reduction and Carotid-IMT
Reduction Per Year
r0.70 , p0.0013
For Each 10 LDL-cholesterol IMT reduction per
year 0.76 (95CI, 0.34-1.18)
Amarenco et al. Stroke 2004352902-9
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Carotid IMT and Metabolic Syndrome
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Carotid IMT and Metabolic Syndrome
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ARIC Carotid IMT Met Synd
Am J Cardiol. 2004941249-54
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First Major Cardiovascular Event in Patients With
Metabolic Syndrome Summary
No. of patients ()
End point
Atorvastatin 80 mg (n2764)
Atorvastatin 10 mg (n2820)
262 (9.5)
367 (13.0)
Major cardiovascular event
46 (1.7)
66 (2.3)
CHD death
139 (5.0)
201 (7.1)
Nonfatal nonPR MI
10 (0.4)
6 (0.2)
Resuscitated cardiac arrest
67 (2.4)
94 (3.3)
Fatal/Nonfatal stroke
HR 0.71 (95 CI 0.61-0.84) Plt0.0001
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ProACTIVE Fatal and nonfatal stroke with
pioglitazone treatment vs placebo in patients
with prior history of stroke
p
Hazard ratio (95 CI)
Placebo, n498
Pioglitazone, n486
End point
0.008
0.53 (0.34 0.94)
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Recurrent stroke
Wilcox RG. World Congress of Cardiology 2006
September 2-6, 2006 Barcelona, Spain.
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Conclusion

• Each component of the metabolic syndrome
  increases the risk of stroke
• Metabolic syndrome is a strong risk factor for
  stroke
• Carotid atherosclerosis and IMT is associated
  with the metabolic syndrome
• Metabolic syndrome could be a target for
  therapeutic trial in prevention of stroke