1. Anticoagulation with warfarin is recommended to prevent recurrent stroke for those with moderate to severe mitral stenosis or mechanical heart valves. 2. The effectiveness of novel oral anticoagulants for stroke prevention in patients with mechanical heart valves is unknown. 3. Routine screening for atrial fibrillation with prolonged rhythm monitoring may be considered for those with bioprosthetic heart valves or mitral valve repair.

1. Secondary Stroke Prevention- 2016
Jonathan Artz, MD
September 8, 2016
Neurology Department Kaiser Permanente San Rafael

2. Objectives
1. Review major factors related to Secondary Stroke
Prevention as emphasized in the recently
updated guidelines for both Kaiser Permanente
Northern California Stroke Care and the American
Heart/Stroke Association.
2. Review key medical management features in
Secondary Stroke Prevention through three
clinical vignettes.
2

3. TIA vs Stroke
TIA: New Definition Is Proposed (2002)
Definition:
Brief episode of neurologic dysfunction caused by focal brain or retinal ischemia
•Clinical symptoms typically lasting less than 1 hour
•No evidence of cerebral infarction (using advanced neuroimaging techniques)
•Urgent brain imaging is recommended
•Albers GW et al. N Engl J Med. 2002;347(21):1713
Rationale :
Traditional definition is out of date and no longer consistent with current
•concepts of brain ischemia
•• Most TIAs are short lived, and advanced imaging techniques may show
•cerebral ischemic injury
3

4. TOAST Classification
1. Large Artery Atherosclerosis
2. Small Vessel Arterial Occlusion/ Ischemia
3. Cardioembolism
4. Other Determined Cause (Venous,Air Embolism).
5. Cryptogenic (Undetermined)
Stroke Vol 24, No 1 January 1993
4

5. 5
Guidelines for the Prevention of Stroke in Patients With
Stroke and Transient Ischemic Attack
A Guideline for Healthcare Professionals From the American Heart
Association/American Stroke Association.
Endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons
(Stroke. 2014;45:00-00.)
http://stroke.ahajournals.org/content/early/2014/04/30/STR.0000000000000024

6. Definitions of Classes and Levels of
Evidence:
AHA/ASA 2014 Stroke Prevention
Guidelines
Class I Evidence or general agreement that procedure or treatment is useful and effective.
Class II Conflicting evidence or divergence of opinion of usefulness/efficacy
Class IIa Weight of evidence or opinion is in favor
Class IIb Usefulness/efficacy is less well established by evidence or opinion
Class III Evidence and/or general opinion that usefulness/effectiveness does not exist and
may be harmful.
LOE A Derived from multiple RCTs
LOE B Derived from a single RCT or nonrandomized studies
LOE C Expert opinion or case series
AHA/ASA = American Heart Association/American Stroke Association
RCT = Randomized Clinical Trial
LOE = Level Of Evidence
6

7. STROKE Recommendations for Evaluation, Treatment,
and Secondary Prevention (Kaiser N-CAL, March 2015)
ENDORSED BY
Chiefs of Emergency Medicine
Chiefs of Medicine
Chiefs of Hospital Medicine
Chiefs of Neurology
Chiefs of Radiology
Chiefs of Cardiology
Chiefs of Vascular Surgery
Medical Director for Quality and Safety
7

8. STROKE Recommendations for Evaluation, Treatment,
and Secondary Prevention (Kaiser N-CAL, March (2015)
ACUTE CARE & SECONDARY PREVENTION TEAM MEMBERS
Jai Cho, MD Neurology, Santa Clara, Clinical Lead
Alexander C. Flint, MD Neuroscience, Redwood City
Jonathan Hartman, MD Neurological Surgery,
Sacramento
Jina Janavs, MD Neurology, Fremont/Hayward
Jeff Klingman, MD Neurology, Walnut Creek
Mai Nguyen-Huynh, MD Neurology, Walnut Creek
8

9. TPMG Clinical Stroke Guidelines
(March,2015)
KP Northern California has adopted the recommendations
from the 2013 AHA/ASA Guidelines for the Early
Management of Patients with Acute Ischemic Stroke and the
2014 AHA/ASA Guidelines for the Prevention of Stroke in
Patients with Stroke and Transient Ischemic Attack, unless
otherwise noted.
References and additional AHA/ASA Guidelines supporting
our recommendations can be found on the Stroke Portal
and linked within the guideline on the KPNC Clinical Library
at:
https://clm.kp.org/pkc/ncal/clib/guidelines/cpg/Stroke_porta
l/index.htm
9

10. What is the Evidence ?
10

11. Risk Factors and Stroke Mechanism
Case #1:
60 year old male awakens from sleep around 1 am following watching the Golden State
Warriors and Cleveland Cavaliers NBA Championship (Game #3). He stands up and drops his
beer can out of his hand and falls to the floor without injury attempting to go the bathroom.
Balance was impaired and he continued to drag his left leg. There was no speech
disturbance, confusion , vision impairment ,sensory disturbance, or headache.
Takes no medications.
Pre notification Stroke Alert called and he is brought in by ambulance to Kaiser SRF E.D.
-Room 3.
Last known normal at end of game which was 11: 00 pm.
No TPA given as his left leg ataxia was not limiting his walking.
NIHSS- 1 ( left lower leg ataxia). ABCD2 score of 4. Initial BP (ER): 160/92. No A.fib on
monitor. BMI- 40%.
Head CT- old right sub-cortical lacunar infarct; Carotid US- 50-69% Left I.C.A. stenosis.
Hospital evaluation: a. No atrial fibrillation on telemetry x 24 hours
b. Brain MRI- no Diffusion Weighted Imaging changes; 2 old lacunar
infarcts and mild microvascular disease.
c. Fasting LDL- 160; Fasting Blood Sugar- 112 (A1C% of 6.4)
d. BP in hospital- 140-164/ 84-96
11

12. Cardiac vs Atherosclerotic
Disease
Case #2
70 year old female with cardiac pacemaker (h/o 3rd
degree heart block) and HTN
noticed abrupt onset of expressive speech disturbance and “confusion” lasting 40
minutes around 3 pm today . No fall, headache,vision disturbance,vertigo,paresis
or gait difficulty. Drove herself in to Kaiser SRF E.D. for evaluation.
Stroke alert not called as event happened 2 hours previously with well defined
normalcy in patient’s and ED MD’s view.
Carotid US done in E.R.- mild atherosclerosis> less 50%- (L)-Internal Carotid Artery
Head CT- normal.
ER BP: 142/92. Heart rate : 112; NIHSS-0; ABCD(2)- 4
Takes 81 mg ASA daily, Lisinopril 20mg a day, Atorvastatin 40mg a day.
Admitted for Observation:
A.Brain MRI- not done (pacemaker)- did not feel study would change
management.
B.BP- held Lisinopril > BP 140-150s systolic and HR in 80-90’s (atrial fib).
C. Fasting LDL- 80; FBS- 94, A1C%- 5.8
12

13. 13

14. Cryptogenic Stroke
Case #3
56 yo female with history of migraine with aura since adolescence, BMI% 32, non
smoker and no history of HTN,dyslipidemia,diabetes nor any personal or family
history of cerebrovascular ,autoimmune or hypercoaguable disorders. Only
medications include imitrex or maxalt (infrequent use). Last migraine 1 month ago.
Awoke from sleep in morning at 6 am with left arm heaviness and numbness
with difficulty walking. Last known well at 1 am when went to sleep. 911 > BIBA to
SRF ED (3). Stroke alert called.
Initial NIHSS of 4 (1 for dysarthria,1 for left arm and leg drift, 1 for sensory
extinction on left).
ED- BP (130/80), pulse of 80-regular, Head CT-negative, CTA (head/neck)- no Large
Vessel Occlusion and no signs of vasculitis or atherosclerosis. Monitor: no afib.
Admission:
Relevant labs: LDL- 100, HDL- 42, FBS-94,A1C% of 5.8, cbc with diff- wnl
PT/INR,PTT- wnl, ANA- normal, hypercoagulable testing (pending)
2. Cardiac: TTE- PFO without atrial septal aneurysm. TEE- consistent with TTE
3. Brain MRI- right sided (acute) single cortical infarct; no white matter disease.
4. Pelvic CT- no DVT; Lower Extremity Dopplers: wnl.14

15. Hypertension
- Initiation of BP therapy is indicated for previously untreated
patients with ischemic stroke or TIA who, after the first
several days, have an established BP ≥140 mm Hg systolic or
≥90 mm Hg diastolic .
(Class I; Level of Evidence B).
- Initiation of therapy for patients with BP <140 mm Hg
systolic and <90 mm Hg diastolic is of uncertain benefit .
(Class IIb; Level of Evidence C).
- For patients with a recent lacunar stroke, it might be
reasonable to target a systolic BP of <130 mm Hg
(Class IIb; Level of Evidence B).
15

16. Dyslipidemia
1. High Intensity Statin therapy with intensive lipid-lowering effects is
recommended to reduce risk of stroke and cardiovascular events
among patients with ischemic stroke or TIA presumed to be of
atherosclerotic origin regardless of recent LDL level.
A. Atorvastatin (Lipitor)- 40-80 mg a day.
B. Rosuvastatin (Crestor)- 20-40 mg a day.
2. Patients with ischemic stroke or TIA and other comorbid ASCVD should
be otherwise managed according to the ACC/AHA 2013 guidelines,
which include lifestyle modifications and dietary recommendations
(DASH Diet).
(Class I; Level of Evidence A).
16

17. High vs Medium Intensity
Statins
High: (Lowers LDL-C by greater than 50%).
1.Atorvastatin (40-80 mg)
2.Rosuvastatin (20-40 mg)
Medium: (Lower LDL-C by 30 to 50%).
1.Atorvastatin (10-20 mg)
2.Rosuvastatin ( 5-10 mg)
3.Simvastatin ( 20-40mg)
4.Pravastatin (40-80mg)
5.Lovastatin (40 mg)
6.Fluvastatin (40 mg PO BID)
7.Pitavastatin (2-4 mg)
Stone NJ et al, American Journal Cardiology ,201317

18. Blood Sugar Control
After a TIA or ischemic stroke, all patients should
probably be screened for DM with testing of fasting
plasma glucose, HbA1c, or an oral glucose tolerance
test.
(Class IIa; Level of Evidence C).
There is no optimal A1C% that is a goal target
specifically for stroke reduction.
18

19. Obesity
1. All patients with TIA or stroke should be screened
for obesity with measurement of BMI.
(Class I; Level of Evidence C).
2. The usefulness of weight loss among patients with
a recent TIA or ischemic stroke and obesity is
uncertain
(Class IIb; Level of Evidence C).
19

20. Physical Activity
For patients who are able and willing to
initiate increased physical activity, referral to
comprehensive, behaviorally oriented
program is probably recommended
(Class IIa; Level of Evidence C).
20

21. Nutrition
1. Look for signs of under or over nutrition and refer as appropriate for nutrition
counseling.
(Class IIa; Level of Evidence C).
2 . Routine supplementation with a single vitamin or combination of vitamins is not
recommended
(Class III; Level of Evidence A).
3. Reduce Sodium intake to less than 1.5 grams/day to lower blood pressure.
(Class IIa; Level of Evidence C).
4. Follow a Mediterranean-type diet instead of a low-fat diet. The Mediterranean-type diet
emphasizes vegetables, fruits, and whole grains and includes low-fat dairy products,
poultry, fish, legumes, olive oil, and nuts. It limits intake of sweets and red meats.
(Class IIa; Level of Evidence C).
21

22. Sleep Apnea
Consider screening for Sleep Apnea for
patients with an ischemic stroke or TIA on the
basis of the very high prevalence of sleep
apnea in this population.
(Class IIb; Level of Evidence B).
22

23. Carotid Disease1. CAS (Carotid Artery Stenting) is indicated as an alternative to CEA (Carotid Endarterectomy) for
symptomatic patients at average or low risk of complications associated with endovascular intervention
when the diameter of the lumen of the internal carotid artery is reduced by >70% by noninvasive imaging
or >50% by catheter-based imaging or noninvasive imaging with corroboration and the anticipated rate of
periprocedural stroke or death is <6%.
(Class IIa; Level of Evidence B).
2. It is reasonable to consider patient age in choosing between CAS and CEA. For older patients (ie, older
than ≈70 years), CEA may be associated with improved outcome compared with CAS, particularly when
arterial anatomy is unfavorable for endovascular intervention. For younger patients, CAS is equivalent to
CEA in terms of risk for peri procedural complication (ie, stroke, MI, or death) and long-term risk for
ipsilateral stroke
(Class IIa; Level of Evidence B).
3. CAS and CEA in the above settings should be performed by operators with established peri procedural
stroke and mortality rates of <6% for symptomatic patients, similar to that observed in trials comparing
CEA to medical therapy and more recent observational studies.
(Class I; Level of Evidence B).
4. Routine, long term follow-up imaging of the extracranial carotid circulation with carotid duplex
ultrasonography is not recommended
(Class III; Level of Evidence B).
5. For patients with recurrent or progressive ischemic symptoms ipsilateral to a stenosis or occlusion of a
distal (surgically inaccessible) carotid artery, or occlusion of a mid cervical carotid artery after institution
of optimal medical therapy, the usefulness of EC/IC bypass is considered investigational .
(Class IIb; Level of Evidence C).
23

24. Intracranial Atherosclerosis
A. For severe stenosis (70%–99%)of a major intracranial artery, consider adding (Plavix) clopidogrel 75
mg/d to aspirin for 90 days might be reasonable.
(Class IIb; Level of Evidence B).
B. For patients with a stroke or TIA attributable to 50% to 99% stenosis of a major intracranial artery,
maintenance of systolic BP below 140 mm Hg and high-intensity statin therapy are recommended.
(Class I; Level of Evidence B)
C. For patients with a stroke or TIA attributable to moderate to severe stenosis (50%–99%) of a major
intracranial artery, angioplasty or stenting is not recommended given the low rate of stroke on medical
management and the inherent peri procedural risk of endovascular treatment
(Class III;Level of Evidence B).
24

25. Atrial Fibrillation
A. Atrial Fibrillation for patients who have experienced an acute ischemic
stroke or TIA with no other apparent cause, prolonged rhythm monitoring
(≈30 days) for AF is reasonable within 6 months of the index event.
(Class IIa; Level of Evidence C)
B.VKA therapy (Warfarin/Coumadin) (Class I; Level of Evidence A)
Apixaban (Class I; Level of Evidence A)
Dabigatran (Class I; Level of Evidence B)
Rivaroxiban (Class IIa, Level of Evidence B)
are all indicated for the prevention of recurrent stroke in patients
with nonvalvular AF, whether paroxysmal or permanent.
25

26. Atrial Fibrillation
A. Can use daily ASA 81 to 325 mg/day) in addition to Warfarin or Novel Oral Anticoagulant
for all patients after ischemic stroke or with clinically apparent CAD, particularly an acute
coronary syndrome or stent placement
(Class IIb; Level of Evidence C).
B. For patients unable to take oral anticoagulants, ASA (325 mg/day) alone is recommended.
(Class IIb; Level of Evidence B).
C. For most patients with a stroke or TIA in the setting of AF initiate oral anticoagulation
within 14 days of CVA/TIA.
(Class IIa; Level of Evidence B).
26

27. Atrial Fibrillation
A. In the presence of high risk for hemorrhagic conversion (ie, large
infarct, hemorrhagic transformation on initial imaging, uncontrolled
hypertension, or hemorrhage tendency), itis reasonable to delay
initiation of oral anticoagulation beyond 14 days.
(Class IIa; Level of Evidence B)
B. The usefulness of closure of the left atrial appendage with the
WATCHMAN device in patients with ischemic stroke or TIA and AF is
uncertain.
(Class IIb; Level of Evidence B).
27

28. Valvular Heart Disease
A. Rheumatic mitral valve disease and AF, long term VKA therapy with an INR target of 2.5
(range, 2.0–3.0) is recommended.
(Class I; Level of Evidence A).
B. Rheumatic mitral valve disease without AF, may consider warfarin rather than
antiplatelet therapy.
(Class IIb; Level of Evidence C).
C. For patients with rheumatic mitral valve disease who have an ischemic stroke or TIA
while being treated with adequate VKA therapy, the addition of aspirin might be
considered.
(Class IIb;Level of Evidence C).
D. Native Aortic or mitral valve disease without AF, antiplatelet therapy is recommended.
(Class I; Level of Evidence C).
28

29. Prosthetic Heart Valve
A. For Mechanical Aortic Valve, VKA (Vitamin K antagonist) therapy is
recommended with an INR target of 2.5 (range, 2.0–3.0)
(Class I;Level of Evidence B).
B. For Mechanical Mitral valve and a history of ischemic stroke or TIA before its
insertion, VKA therapy is recommended with an INR target of 3.0 (range, 2.5–3.5)
(Class I;Level of Evidence C).
C. For patients with a mechanical mitral or aortic valve who have a history of
ischemic stroke or TIA before its insertion and who are at low risk for bleeding, the
addition of aspirin 75 to 100 mg/d to VKA therapy is recommended.
( Class I; Level of Evidence B).
D. Patients with bioprosthetic aortic or mitral valve, a history of ischemic stroke
or TIA before its insertion, and no other indication for anticoagulation therapy
beyond 3 to 6 months from the valve placement, long-term therapy with aspirin
75 to 100 mg/d is recommended in preference to long-term anticoagulation
(Class I; Level of Evidence C).
29

30. Antiplatelet Therapy
A.For High Risk TIA (ABCD2 score 4 or greater) and any stroke, the combination of
ASA (81-162 mg/day) and Clopidogrel (75 mg/day) might be considered for
initiation within 24 hours of a minor ischemic stroke or TIA and for continuation of
90 days.
CHANCE STUDY (CHINA)
POINT TRIAL (ONGOING in USA).
(Class IIb; Level of Evidence B).
A.For patients with a history of ischemic stroke or TIA, AF, and CAD, the usefulness
of adding antiplatelet therapy to VKA therapy is uncertain for purposes of
reducing the risk of ischemic cardiovascular and cerebrovascular events.
(Class IIb; Level of Evidence C).
30

31. Aortic Arch Atheroma(s)
A. For patients with an ischemic stroke or TIA and evidence of aortic arch
atheroma, antiplatelet therapy is recommended.
(Class I; Level of Evidence A).
B. For patients with an ischemic stroke or TIA and evidence of aortic arch
atheroma, statin therapy is recommended.
(Class I; Level of Evidence B).
NO PRESENT EVIDENCE FOR USE OF
ANTICOAGULANTS or SURGICAL ENDARECTOMY.
31

32. Patent Foramen Ovale (PFO)
32
A. For ischemic stroke or TIA and a PFO, antiplatelet therapy is recommended
(Class I; Level of Evidence B).
B. For patients with an ischemic stroke or TIA and both a PFO and a venous
source of embolism, anticoagulation is indicated, depending on stroke
characteristics.
(Class I; Level of Evidence A).
C. When anticoagulation is contraindicated, an inferior vena cava filter is
reasonable.
(Class IIa; Level of Evidence C).
D. For cryptogenic ischemic stroke or TIA and a PFO without evidence for DVT,
available data do not support a benefit for PFO closure.
(Class III; Level of Evidence A).
E. In the setting of PFO and DVT, PFO closure by a transcatheter device might be
considered, depending on the risk of recurrent DVT.
(Class IIb; Level of Evidence C).

33. Case #1- Management and Long Term Risk Reduction
A. Hypertension: start ACE Inhibitor, Calcium Channel Blocker or
Diuretic with outpatient BP checks consistently and daily over
coming weeks.
Goal BP under 130/90.
B. Statin: check baseline ALT and begin High Intensity Statin such as
Atorvastatin (40-80 mg a day)- other options (Rosuvastatin 20-40
mg a day).
Recheck Fasting Lipid Panel in 2-3 months> goal LDL under 80 and
preferably 50% reduction of LDL level.
C. Nutrition: DASH Diet- low sodium (under 1.5 grams per day) with
focus on Fruits/Vegetables as described in Mediterranean lifestyle
concept.
D. Exercise: 30-45 minutes (moderate aerobic exercise)- jogging or
equivalent to get Heart Rate to aerobic zone (220-age= # x 0.65%) 5
days per week or equivalent of 150 minutes of exercise a week.
E. 81 to 162 mg ASA OR 3 weeks of 75 mg Clopidrogrel and 81-162 mg
ASA followed by Clopidrogrel monotherapy (75 mg a day).
F. Obstructive Sleep Apnea screen.33

34. CHANCE STUDY
Clopidogrel with Aspirin in Acute Minor Stroke or
Transient Ischemic Attack
N Engl J Med 2013; 369:11-19July 4, 2013
Results: Stroke occurred in 8.2% of patients in the clopidogrel–aspirin group, as
compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence
interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients
(0.3%) in the clopidogrel–aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the
rate of hemorrhagic stroke was 0.3% in each group
Conclusions:
Among patients with TIA or minor stroke who can be treated within 24
hours after the onset of symptoms, the combination of clopidogrel and
aspirin is superior to aspirin alone for reducing the risk of stroke in the
first 90 days and does not increase the risk of hemorrhage
Treatment: Clopidogrel at an initial dose of 300 mg,
followed by 75 mg per day for 90 days, plus aspirin at a dose
of 75 mg per day for the first 21 days.34

35. Case #2- Management and Long Term Risk
Reduction
A. Hypertension: Restart Lisinopril and may have to increase dose to 40 mg a
Day with outpatient daily monitoring over coming weeks. ( check potassium and
creatinine levels).
Goal BP under 130/90 long term.
B. Statin: check baseline ALT and continue High Intensity Statin such as
Atorvastatin increasing to 60 mg a day.
C. Recheck Fasting Lipid Panel in 2-3 months> goal LDL under 70 mg/dl and
50% reduction of LDL level.
C. Nutrition: DASH Diet- low sodium (under 1.5 grams per day) with focus on
Fruits/Vegetables as described in Mediterranean lifestyle concept.
D. Exercise: 30-45 minutes (moderate aerobic exercise)- jogging or equivalent
to get Heart Rate to aerobic zone (220-age= # x 0.65%) 5 days per week or
equivalent of 150 minutes of exercise a week.
E. Start 325 mg ASA orally with Coumadin (INR goal 2.0 to 3.0) and stop ASA
when INR is > 2.0 or Novel Oral Anticoagulant such as Pradaxa.
F. Follow up Carotid Ultrasound in 6-12 months (re examine Left I.C.A.)
35

36. Anticoagulation After Cardioembolic
Stroke: To Bridge or Not to Bridge?
• Hen Hallevi, MD,1
Karen C. Albright, DO, MPH,3
Sheryl
Martin-Schild, MD, PhD,1
Andrew D. Barreto, MD,1
Sean I. Savitz, MD,1
Miguel A. Escobar, MD,2
Nicole R.
Gonzales, MD,1
Elizabeth A. Noser, MD,1
Kachi Illoh,
MD,1
and James C. Grotta, M
Arch Neurol. 2008 Sep; 65(9): 1169–1173.
Conclusion: Anticoagulation of patients with cardio
embolic stroke can be safely started with warfarin
shortly after stroke. Heparin bridging and enoxaparin
bridging increase the risk for serious bleeding
36

37. Case #3- Management and Long Term Risk
Reduction
A. Hypertension: Consider low dose ACE inhibitor , Diuretic or Calcium Channel
blocker.
This recommendation is based upon observations in randomized trials, such as
PROGRESS, that the relative risk reduction in stroke with antihypertensive
therapy was similar at all levels of baseline systolic pressure (ranging from
<120 to ≥160 mmHg).
Lower target blood pressures are safe and effective for the prevention of recurrent stroke: the PROGRESS trial. AUArima H,
Chalmers J, Woodward M, Anderson C, Rodgers A, Davis S, Macmahon S, Neal B, PROGRESS Collaborative GroupSO
J Hypertens. 2006;24(6):1201.
Goal BP under 130/90 long term.
B. Statin: check baseline ALT and start High Intensity Statin such as Atorvastatin
(40-80) mg a day.
-Recheck Fasting Lipid Panel in 2-3 months> goal LDL under 70 mg/dl and 50%
reduction of LDL level.
C. Exercise: 30-45 minutes (moderate aerobic exercise)- jogging or equivalent
to get Heart Rate to aerobic zone (220-age= # x 0.65%) 5 days per week or
equivalent of 150 minutes of exercise a week.
D. Start 325 mg ASA orally with Coumadin (INR goal 2.0 to 3.0) and stop ASA
when INR is > 2.0 or long term Novel Oral Anticoagulant such as Pradaxa.
E Long term monitoring session for atrial fibrillation detection.37

38. Thanks for Helping
38
REDUCE STROKE RISK