Update on the Primary Prevention of Ischemic Stroke

8/4/2019 Update on the Primary Prevention of Ischemic Stroke

1/33

Update on the PrimaryUpdate on the Primary

Prevention of Ischemic StrokePrevention of Ischemic Stroke

AHA/ASA GuidelinesAHA/ASA Guidelines

Jennifer M. Ferguson, MDJennifer M. Ferguson, MD


2/33

ObjectivesObjectives

11. The attendee should be able to identify. The attendee should be able to identify

the risk factors for ischemic stroke.the risk factors for ischemic stroke.22. The attendee should be able to. The attendee should be able tounderstand the current treatmentunderstand the current treatmentguidelines for the modifiable risk factors:guidelines for the modifiable risk factors:

Hypertension, Diabetes,Hypertension, Diabetes, DyslipidemiaDyslipidemia,,Smoking, andSmoking, and AtrialAtrial Fibrillation.Fibrillation.

33. The attendee should be able to. The attendee should be able tounderstand the impact of lifestyleunderstand the impact of lifestyle

modification, diet, nutrition and weightmodification, diet, nutrition and weightcontrol in the prevention of ischemiccontrol in the prevention of ischemicstroke.stroke.


3/33

Ischemic Stroke CausesIschemic Stroke Causes

Large arteryLarge artery

atherosclerosisatherosclerosis13%13%

Small arterySmall artery

occlusionocclusion 23%23%CardioembolismCardioembolism27%27%

Undetermined orUndetermined orCryptogenicCryptogenic 35%35%

OtherOther 2%2%


4/33

Subtypes of brain ischemiaSubtypes of brain ischemia

ThrombosisThrombosis

EmbolismEmbolism

HypoperfusionHypoperfusion


5/33

Characteristics of Ischemic StrokeCharacteristics of Ischemic Stroke

SubtypesSubtypes

ThrombosisThrombosis Local obstruction of an artery (arteriosclerosis, dissection,Local obstruction of an artery (arteriosclerosis, dissection,

fibromuscularfibromuscular dysplasiadysplasia)) Large or small vessel diseaseLarge or small vessel disease

Symptoms often fluctuate, remit or progress in a stutteringSymptoms often fluctuate, remit or progress in a stutteringfashionfashion

EmbolismEmbolism Particles of debris from another source (heart, aorta, largeParticles of debris from another source (heart, aorta, large

vessels) which blocks arterial accessvessels) which blocks arterial access

Symptoms abrupt and maximal at onsetSymptoms abrupt and maximal at onset

HypoperfusionHypoperfusion More global circulatory problem (brain or other organs)More global circulatory problem (brain or other organs)

Reduced arterial blood flowReduced arterial blood flow

Symptoms typically diffuse andSymptoms typically diffuse and nonfocalnonfocal with bilateralwith bilateral neuroneurosigns commonsigns common


6/33

Framingham Stroke ProfileFramingham Stroke Profile

Assesses risk at primary care levelAssesses risk at primary care level

Utilizes nine factors in the risk profileUtilizes nine factors in the risk profile

Sex ,age, SBP, antihypertensiveSex ,age, SBP, antihypertensive

treatment, diabetes, smoking,treatment, diabetes, smoking,cardiovascular disease,cardiovascular disease, afibafib, and LVH, and LVH

Calculates absolute stroke risk over aCalculates absolute stroke risk over a

given period of timegiven period of timeItIts the best we have for nows the best we have for now


7/33

NonmodifiableNonmodifiable Risk FactorsRisk Factors

AgeAge

GenderGender

Race/EthnicityRace/Ethnicity

Family historyFamily history

Genetic factorsGenetic factors

Low birth weightLow birth weight


8/33

Modifiable Risk FactorsModifiable Risk Factors

HypertensionHypertension

DiabetesDiabetes

DyslipidemiaDyslipidemia

AFibAFib

SmokingSmoking

ObesityObesity

Physical inactivityPhysical inactivity

DietDiet


9/33

Potentially Modifiable Risk FactorsPotentially Modifiable Risk Factors

MetabolicMetabolic

SyndromeSyndromeDrug and AlcoholDrug and Alcohol

AbuseAbuse

Sleep ApneaSleep Apnea

Elevated LpElevated Lp--PLA2PLA2

ElevatedElevated LpaLpa

InflammationInflammation

InfectionInfection

MigraineMigraine

headachesheadaches

HypercoaguableHypercoaguable

disordersdisorders

OralOral

ContraceptivesContraceptives

ElevatedElevated

homocysteinehomocysteine


10/33

HypertensionHypertension

Single most important treatable risk factorSingle most important treatable risk factor

Reduction in BP associated with aReduction in BP associated with a 3030--40%40%decrease in stroke incidencedecrease in stroke incidence

Treatment must be individualizedTreatment must be individualized Goal is


11/33

Dihydropyridine calcium channel blockerRaynaud's syndrome

Beta blockerPerioperative hypertension

Thiazide diureticOsteoporosis

Beta blocker, calcium channel blockerMigraine

Beta blockerHyperthyroidism

Beta blocker (noncardioselective)Essential tremor

Alpha blockerBenign prostatic hypertrophy

Likely to have a favorable effect on symptoms in comorbid

conditions

Beta blocker, nondihydropyridine calcium channel

blockerAtrial flutter rate control

Beta blocker, nondihydropyridine calcium channel

blockerAtrial fibrillation rate control

Beta blocker, calcium channel blockerAngina pectoris

Diuretic (ALLHAT), perhaps ACE inhibitor (HOPE)Diabetes mellitus (no proteinuria)

Diuretic (ALLHAT), perhaps ACE inhibitor (HOPE)High coronary disease risk

ACE inhibitor and/or ARBProteinuric chronic renal failure

ACE inhibitor, beta blocker, aldosterone antagonistPost-myocardial infarction

ACE inhibitor or ARB, beta blocker, diuretic,

aldosterone antagonist*Systolic heart failure

Compelling indications (major improvement in outcomeindependent of blood pressure)

Antihypertensive drugsIndication

Considerations for individualizing antihypertensive therapy


12/33

Considerations for individualizing antihypertensive therapyConsiderations for individualizing antihypertensive therapy

ACE inhibitor or ARBRenovascular disease

Thiazide diureticHyponatremia

Aldosterone antagonist, ACE inhibitor, ARBHyperkalemia

DiureticGout

Beta blocker, central alpha agonistDepression

May have adverse effect on comorbid conditions

Beta blocker, nondihydropyridine calcium channel blockerSecond or third degree heart block

ACE inhibitor, ARB (includes women likely to become

pregnant)Pregnancy

MethyldopaLiver disease

ReserpineDepression

Beta blockerBronchospastic disease

ACE inhibitorAngioedema

Contraindications

A survival benefit from an aldosterone antagonist has only been demonstrated in patients with advanced heartfailure; in patients with less severe disease, an aldosterone antagonist is primarily given for hypokalemia

Adapted from The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, andTreatment of High Blood Pressure, JAMA 2003; 289:2560.


13/33

DiabetesDiabetes

1515--33% of patients with ischemic stroke33% of patients with ischemic stroke

ADA recommends all patients be treatedADA recommends all patients be treatedwith andwith and ACEACE--I or ARBI or ARB

Goal is to treat HTN,Goal is to treat HTN, dyslipidemiadyslipidemia,,

microalbuminuriamicroalbuminuria and hypoglycemia usingand hypoglycemia usingmultifactorialmultifactorial approach including diet,approach including diet,

exercise, oralexercise, oral hypoglycemicshypoglycemics and insulinand insulin

Tight control reducesTight control reduces microvascularmicrovascularcomplicationscomplications


14/33

Definitions and GoalsDefinitions and Goals

Normal=FBS 60Normal=FBS 60--100mg/dl100mg/dl

IFG=100IFG=100--126mg/dl (glucose126mg/dl (glucose

intolerance)intolerance)

Diabetes=FBS greater thanDiabetes=FBS greater than126mg/dl or a random BS greater126mg/dl or a random BS greater

than 200mg/dlthan 200mg/dl

HgA1c less than 7%HgA1c less than 7%


15/33

Treatment OutcomesTreatment OutcomesHgA1c less thanHgA1c less than 7%7% reduces the risk ofreduces the risk ofmicrovascularmicrovascular andandpossiblepossible macrovascularmacrovascular complicationscomplications

UK Prospective Diabetes Study showed that a reduction inUK Prospective Diabetes Study showed that a reduction inA1c byA1c by 1%1% reduced ischemic stroke risk byreduced ischemic stroke risk by 15%15%

ACEACE--I/I/ARBsARBs affect progression of diabetic nephropathy andaffect progression of diabetic nephropathy andreducereduce albuminuriaalbuminuria

DCCT revealed that tight control of BS in Type I and Type IIDCCT revealed that tight control of BS in Type I and Type II

DM reducedDM reduced microvascularmicrovascular complicationscomplicationsFatal and nonfatal CV events were reduced in Type I DMFatal and nonfatal CV events were reduced in Type I DM

Jury is still out on Type II DM (ACCORD Study) whereJury is still out on Type II DM (ACCORD Study) whereintensive control of blood sugar in Type II diabetics (with aintensive control of blood sugar in Type II diabetics (with ahigh risk of CAD) had a higher rate of mortalityhigh risk of CAD) had a higher rate of mortality


16/33

Oral agents and Insulin forOral agents and Insulin for

treatment of diabetestreatment of diabetesInsulins Generic Trade name

Onset of

Action

Peak of

Action

Duration

of Action

Lispro

Aspart

Humalog

Novolog 515min 12h 35h

Regular

HumulinR

Novolin R 3060min 24h 68h

Intermediate

actingNPH Novolin N

Humulin N 13h 57h 1318h

Ultralente 24h 814h 1830h

Glargine Lantus Within 4h Peakless >24h

Mixed Novolin 70/30

Rapid acting

Long acting

Class of Agents Agents Trade Name Mechanism of Action

Glipizide Glucotrol

Glyburide

Diabeta,

Glynase,

Micronase

Glimepiride Amaryl

Nateglinide Starlix

Repaglinide Prandin

Biguanides Metformin Glucophage Insulin sensit izer (liver)

Pioglitaz one Ac tos

Rosigl itazone Avandia

Acarbose Precose

Miglitol Glyset

-glucosidase

inhibitors

Insulin secretagogues

Delay glucose absorption

by antagonizing enzymes

Insulin sensitizer (skeletal

muscle)

Postprandial insulinsecretagogues

Sulfonylureas

Metglitinides

Thiazolidinediones


17/33

DyslipidemiaDyslipidemiaClearly an established risk factor for CADClearly an established risk factor for CAD

but not so for first or recurrent strokebut not so for first or recurrent strokeRisk reduction inRisk reduction in statinstatin trials may be fortrials may be fornonfatal stroke (risk was reduced 21nonfatal stroke (risk was reduced 21--29%29%for first or recurrent stroke)for first or recurrent stroke)

Patients with ischemic stroke secondary toPatients with ischemic stroke secondary toatherosclerosis are good candidates for aatherosclerosis are good candidates for astatinstatin

Goal LDL < 100mg/dlGoal LDL < 100mg/dl

Patients withPatients with low HDLlow HDL and ischemic strokeand ischemic strokemay be good candidates formay be good candidates for niacinniacin ororgemfibrozilgemfibrozil


18/33

Treatment OptionsTreatment OptionsStatinsStatinsLovastatinLovastatin

PravastatinPravastatin

SimvastatinSimvastatinFluvastatinFluvastatin

AtorvastatinAtorvastatin

RosuvastatinRosuvastatin

GemfibrozilGemfibrozil

FenofibrateFenofibrateNicotinic AcidNicotinic Acid

Bile acidBile acid sequestrantssequestrantsCholestyramineCholestyramine

CholestipolCholestipolColesevelamColesevelam

Cholesterol absorption inhibitorsCholesterol absorption inhibitorsEzetimibeEzetimibe

NeomycinNeomycin

ProbucolProbucol


19/33

Adult treatment panel III classificationAdult treatment panel III classification

of LDL, total, and HDL cholesterolof LDL, total, and HDL cholesterol

High60 (1.55)

Low


20/33

AtrialAtrial Fibrillation (AF)Fibrillation (AF)

ValvularValvular

NonvalvularNonvalvular

Persistent and paroxysmal AF arePersistent and paroxysmal AF are

strong predictors of first and secondstrong predictors of first and secondstrokestroke

AF accounts forAF accounts for 20%20% of ischemicof ischemic

strokesstrokes


21/33

CHADS2 scoreCHADS2 scoreCCHFHF

HHTNTNAAgege

DDMM

SSecondary preventionecondary prevention

in pts with priorin pts with priorischemic stroke or TIAischemic stroke or TIAor systemic embolicor systemic emboliceventevent

The CHADS2 scoreThe CHADS2 scoreestimates the risk ofestimates the risk ofstroke instroke in warfarinwarfarinversus noversus no warfarinwarfarintreatment groups intreatment groups inpatients withpatients with

nonvalvularnonvalvular AF.AF.WarfarinWarfarin treatmenttreatmentgroup results weregroup results werestatistically significantstatistically significantin primary preventionin primary preventionof ischemic stroke.of ischemic stroke.


22/33

Lifestyle Modification and Impact onLifestyle Modification and Impact on

Reduction of Ischemic StrokeReduction of Ischemic Stroke

Obesity/Weight LossObesity/Weight LossSmoking CessationSmoking Cessation

Alcohol AbuseAlcohol Abuse

ExerciseExercise

Diet and NutritionDiet and Nutrition


23/33

Obesity/Weight LossObesity/Weight Loss

DefinitionsDefinitions

BMIBMI is a measure of body fat based onis a measure of body fat based onheight and weightheight and weight

ObeseObese Waist circumference > 40 inches in males, >Waist circumference > 40 inches in males, >

35 inches in females, BMI >30kg/m235 inches in females, BMI >30kg/m2 Goal BMI


24/33

Metabolic SyndromeMetabolic SyndromeCurrent ATP III criteria define the metabolic syndrome asCurrent ATP III criteria define the metabolic syndrome asthe presence of any three of the following five traits:the presence of any three of the following five traits:

Abdominal obesityAbdominal obesity, defined as a waist circumference in men, defined as a waist circumference in men>102 cm (40 in) and in women >88 cm (35 in)>102 cm (40 in) and in women >88 cm (35 in)

Serum triglyceridesSerum triglycerides 150 mg/150 mg/dLdL (1.7(1.7 mmolmmol/L) or drug/L) or drugtreatment for elevated triglyceridestreatment for elevated triglycerides

Serum HDL cholesterolSerum HDL cholesterol


25/33

SmokingSmokingBelieved to increase stroke by generation ofBelieved to increase stroke by generation ofthrombus in previously narrowed arteriesthrombus in previously narrowed arteries

((increases atherosclerosisincreases atherosclerosis))Multiple studies show increase inMultiple studies show increase in ischemicischemic andandhemorrhagic strokehemorrhagic stroke ((22--foldfold))

Framingham revealed that heavy smokers (>40Framingham revealed that heavy smokers (>40

cigs/day) hadcigs/day) had two timestwo times the risk of strokethe risk of stroke vsvs lightlightsmokers (


26/33

PharmacotherapyPharmacotherapy

NonNon--nicotine based Therapynicotine based TherapyBupropionBupropion HCl/WellbutrinHCl/Wellbutrin May be used in combination with patch for greater efficacyMay be used in combination with patch for greater efficacy

Provides therapy for coProvides therapy for co--morbid depression (antimorbid depression (anti--smokingsmokingeffect independent of this)effect independent of this)

Use relatively contraindicated in smokers with a history ofUse relatively contraindicated in smokers with a history ofseizures, head trauma, heavy alcohol abuse, or anorexiaseizures, head trauma, heavy alcohol abuse, or anorexia

Multiple drugMultiple drug--drug interactions, esp. with antidrug interactions, esp. with anti--HIV medsHIV meds

300 mg/day (in 2 divided doses to minimize side effects)300 mg/day (in 2 divided doses to minimize side effects)

StartStart two w eekstwo weeks prior to anticipated quit date and continueprior to anticipated quit date and continuefor 7 to 12 weeksfor 7 to 12 weeks

Optimal duration of treatment not well definedOptimal duration of treatment not well defined

Varenicline/ChantixVarenicline/Chantix One 0.5 mg tablet daily for three days, one 0.5 mg tabletOne 0.5 mg tablet daily for three days, one 0.5 mg tablet

twice daily for the next four days, one 1 mg tablet twice dailytwice daily for the next four days, one 1 mg tablet twice dailystarting at day seven.starting at day seven.


27/33

PharmacotherapyPharmacotherapy

Nicotine based TherapyNicotine based TherapyNicotineNicotine polacrilexpolacrilex (gum or lozenge)(gum or lozenge)

Accessible overAccessible over--thethe--countercounter

May satisfy oral behaviorMay satisfy oral behavior

Requires multiple dosing, thus, compliance may be affectedRequires multiple dosing, thus, compliance may be affected Start on quit date


28/33

ETOHETOHLight to moderate alcohol (


29/33

Exercise/Diet/NutritionExercise/Diet/NutritionCDC and NIH recommend 30 minutes of vigorousCDC and NIH recommend 30 minutes of vigorousactivity (brisk walking) 4activity (brisk walking) 4--6X/week6X/week

DASH dietDASH diet (Dietary Approaches to Stop HTN)(Dietary Approaches to Stop HTN)designed to reduce blood pressure, cholesteroldesigned to reduce blood pressure, cholesteroland improve insulin sensitivityand improve insulin sensitivity

DASH diet associated with lower rate of strokeDASH diet associated with lower rate of stroke

and MI in healthy womenand MI in healthy womenSupplements and Dietary fat (Supplements and Dietary fat (VitVit E, C, Fish Oils,E, C, Fish Oils,and Fat intake) are controversial in strokeand Fat intake) are controversial in strokepreventionprevention

Reduced sodium (4.7g/d) in patients with HTNwithout CKD reduces riskwithout CKD reduces risk


30/33

SummarySummary700,000700,000 Strokes/year in USAStrokes/year in USA

80%80% of all strokes areof all strokes are ischemicischemic,, 20%20% areare hemorrhagichemorrhagic

The main subtypes of ischemic stroke are due toThe main subtypes of ischemic stroke are due to thrombusthrombus,,embolusembolus, or, or hypoperfusionhypoperfusion

MajorMajor modifiablemodifiable risk factorsrisk factors HTNHTN

DiabetesDiabetes

DyslipidemiaDyslipidemia AfibAfib

SmokingSmoking

AlcoholAlcohol

Obesity/Metabolic SyndromeObesity/Metabolic Syndrome

Sedentary LifestyleSedentary LifestyleTreatment and control of risk factors by the primary careTreatment and control of risk factors by the primary carephysician will reduce the overall incidence of ischemicphysician will reduce the overall incidence of ischemicstrokestroke


31/33

Stroke WorkStroke Work--upupMEDICALMEDICAL TESTTEST

STARESTARE INTO THE CAT'S EYESINTO THE CAT'S EYES FORFOR 1010SECONDSSECONDS ......


32/33

Stroke WorkStroke Work--upupNOWNOW STARE IN THE PUPPY'SSTARE IN THE PUPPY'S

EYES FOR 10EYES FOR 10 SECONDSSECONDS ......


33/33

Stroke WorkStroke Work--upupYourYour CAT SCAN and LABCAT SCAN and LABTESTS are COMPLETE!TESTS are COMPLETE!

Sorry,couldntresist!

Update on the Primary Prevention of Ischemic Stroke

Documents

Transcript of Update on the Primary Prevention of Ischemic Stroke