Thursday, June 14, 2001 Congress of Epidemiology 2001Toronto, Canada 1 Stroke Epidemiology-2001...

Thursday, June 14, 2001

Congress of Epidemiology 2001Toronto, Canada

Stroke Epidemiology-2001

Aurora K. Pajeau, M.D., MPHStroke Director

LSUHSC-Shreveport

Stroke-2001

• 3rd leading cause of death in the United States

• A major cause of disability among adults.

• Estimated 750,000 annual incident strokes.

• >4 million stroke survivors.

Well-Documented Modifiable

Stroke Risk Factors

HTN (Age 50-80) 20-55% 40-20 4.0-1.4 38%

Smoking 25% 12-18 1.8 50% /c 1yr

DM 20% 14-58 1.8-6 /c BP Asxto Carotid Stn 2-8% 2-7 2.0 50%

TC men 55y 25% 25 1.8/ 240-279 20-30% women 65y 40% 2.6/>280 /c statinsA Fib 0.5-8.8% 1.5-23 5 2.6-4.5 68% A/C

21%ASAAdapted from Goldstein et al: Stroke 2001;32:280-299

Factor Prevalence PAR% RR %Risk /c Tx

Hyperlipidemia

~36% (60x106) adults in U.S.

Mean TC levels increase in men till age 55-64 then decline.

25% of American men and 28% of women have TC levels >240mg/dl (6.21mm/l)

Normal Endothelium

Fibrous Plaque

Stimuli Initiating Atherosclerosis

Hypertension Mechanical forces, sheer stress response

Oxidized LDL Adhesion, permeability, deposition

Homocysteine[O] LDL, vascular toxin

Cigarettes Toxic, oxidizing glycation products

Hyperglycemia Arterial retention of Trigl

Infection Vessel wall injury

Novel Risk Factors

• Hyperhomocysteinemia

• Infection and inflammation

• Additional genetic factors– Hemostatic and coagulation disorders

• Leisure time inactivity and obesity

• Fast food restaurant abuse

• Second hand smoke

Hyperhomocysteinemia

• HC is a highly reactive amino acid toxic to vascular endothelium– Pro-atherogenic and pro-thrombotic effect on

blood vessels

• HC can potentiate the auto-oxidation of LDL

• HC is emerging as a potentially modifiable risk factor for atherosclerosis

Infection and Inflammation

• Infectious agents contribute to initiation and chronic formation, progression and activation of atherosclerotic plaques.

• Infectious agents can be seen as triggers

Infection and Inflammation

Chlamydia pneumoniae Helicobacter pylori

• Cytomegalovirus

• Herpes virus Periodontal disease Genetic influence

Chlamydia Pneumoniae

• Obligate intracellular parasite Infects mononuclear phagocytes

• Macrophages derived from them localize in atherosclerotic plaque to provide mechanism for entry of organism into vessel wall

Helicobacter pylori

• Thought to be a potential factor in causing pathophysiology of atherosclerosis

• One strain was found to be associated with increased cytokine expression.

Periodontal Disease

• A mechanism for chronic systemic inflammation from Gm (-) organisms

• Advanced disease estimated prevalence:– 15% -60-64 yo– >45% in >65 y.o.

• One study showed a significant ischemic stroke risk (RR 2.1) among those with periodontitis.

Genetic Inflammatory Disorders

• Genetic mutations & gene polymorphisms

– Associated with inflammatory pathways– May lead to increased susceptibility to

develop atherosclerosis– Particular HLA types

Genetic Inflammatory Disorders

• Continuing research in linkage analysis studies and association studies with genetic influence based on risk factor exposure are needed.

Genetic Hemostatic & Coagulation Factors

• Sickle cell disease

• CADASIL

• Coagulation disorders

• Connective tissue disorders

• Vasculopathies

• Metabolic disorders

CADASIL

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopahty– monogenic inherited small vessel disease– Notch 3 gene on chromosome 19q12– Migraines, TIAs, lacunar strokes– Stroke and dementia in early middle age

Fast Food Restaurant Abuse

• Increased trans fatty acid intake from foods fried in partially hydrogenated fats at fast food restaurants– Trans unsaturated fatty acids LDL and HDL– Major contributor is hydrogenated fats

• Builds plaque in arteries

Leisure Time Inactivity and Obesity

• Obesity defined as BMI>30kg/m2

with age– Associated with BP, glucose, lipids*

*Walker et al: Am J Epi 1996

Guidelines for Stroke Prevention

• Antiplatelets & anticoagulation

• HTN control

• Statin agents

• RAAS inhibition

• Leisure time activity

• Dietary guidelines

Guidelines for Stroke Prevention

Aspirin and Sub Q heparin for inpatient with acute stroke

IV heparin for TIA from symptomatic carotid stenosis, until CEA

Bottom line: ASA/ext. release dipyridamole better than aspirin alone, may be better than clopidogrel

Use of Anticoagulant Therapy

• Coagulopathies (INR 2-3), prosthetic heart valves( INR 2.5-3.5)

• Nonvalvular atrial fibrillation (INR 2-3)– Age <65, no risk factors Aspirin– Age <65, /c risk factors Warfarin– Age 65-75, no risk factors Aspirin or Warfarin– Age 65-75 /c risk factors Warfarin– Age >75, /c or /s Warfarin

Hypertension Control

• SBP<140mmHg & DBP<90mmHG

• <135/<85 if target organ damage

• Antihypertensive medications

• Lifestyle modification

Leisure Time Inactivity and Obesity

• Walking AM &PM 1.8 mi/d most days of week will modify risk of cardiovascular disease and stroke**.

*Walker et al: Am J Epi 1996; **Rexrode et al:JAMA 1997.**Abbott RD et al: Am J Epi 1994

Leisure Time Activity

• Exercise will insulin resistance, fibrinogen, LDL and weight and will HDL

– There is no dose relationship with level of activity

Novel Approaches to Stroke Prevention

• Statin agents used for hyperlipidemia may reduce risk of stroke*.

• Antihypertensive agents that inhibit the renin-angiotensin –aldosterone system (RAAS) may reduce risk by non-hypertensive lowering mechanisms**.

*Plehn et al: Circ 1999; LIPID Study Gp: N Engl J Med 1998

**Van Bortel et al: Am J Card 1995; Thybo et al: HTN 1995

Stroke Prevention Therapy

• AHA Dietary Guidelines, 2000*– General population– Special populations– Ancillary lifestyle issues

• BMI120% of ideal body weight for height

Krauss et al, Stroke 2000.

Physician-Community Knowledge Gap

• Well-defined stroke prevention measures underutilized, misapplied

• Knowledge of risk factors for primary stroke prevention– CME, physician recertification– Promote stroke prevention legislation

U.S. Legislative Measures

• Public education and awareness of stroke• Improved stroke care• Kennedy Bill

– Establish a national clearinghouse on stroke treatment & research

– Authorize a national public awareness and education plan

– Provide state grants to ensure stroke patients have access to high quality care

STOP Stroke Act

• Stroke Treatment and Ongoing Prevention• Public awareness campaign• Grant program• Ensure training in prevention & treatment for

medical personnel• Create comprehensive research for best

practices, barriers, disparities; measure effect of public awareness efforts.

STOP Stroke Act

Stroke legislation hot line:

www.stroke.org/strokesmart.cfm

Thursday, June 14, 2001 Congress of Epidemiology 2001Toronto, Canada 1 Stroke Epidemiology-2001...

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