ASA/AHA 2014 guidelines for the Primary Prevention of Stroke Hypertension and dyslipidemia impact on stroke development and prevention SPRINT and HOPE-3

1. Primary prevention of
Stroke
Usama Ragab Yousif (Msc.)
Internal Medicine Department
2/01/2017 (Monday)

2. Agenda
• Hypertension and dyslipidemia impact on stoke
development and prevention
• SPRINT and HOPE-3
• ASA/AHA 2014 guidelines for the Primary Prevention of
Stroke

3. Epidemiology
• Globally, about 17
million strokes occur
every year and stroke is
the second leading
cause of death after
coronary heart disease,
and the third most
common cause of
disability.
1- Krishnamurthi RV: Lancet Glob Health. 2013;1(5):e259.
Figure: http://www.who.int/mediacentre/factsheets/fs310/en/

5. Polypill concept
BMJ. 2003 Jun 28; 326(7404): 1419.
• The Polypill strategy could largely prevent heart attacks and stroke if
taken by everyone aged 55 and older and everyone with existing
cardiovascular disease.
Simvastatin , hydrochlorothiazide, atenolol,
enalapril, folic acid, and aspirin

6. Polypill concept
Circulation. 2010;122:2078-2088.

8. Risk factors for stroke
POTENTIALLY Modifiable risk factorsFixed risk factors
Blood pressure
Cigarette smoking
Hyperlipidaemia
Heart disease
Atrial fibrillation
Congestive cardiac failure
Infective endocarditis
Diabetes mellitus
Excessive alcohol intake
Oestrogen-containing drugs
Polycythaemia
Age
Gender (male > female except at
extremes of age)
Race (Afro-Caribbean > Asian >
European)
Previous vascular event
 Myocardial infarction
 Stroke
Peripheral vascular disease
Heredity
High fibrinogen
P, Langhorne. "Stroke Disease." Davidson’s Principles and Practice of Medicine. 22nd ed. N.p.: Elsevier, 2014. 1231-248. Print.

9. Risk factors for stroke (cont.)
TIA is a risk factor for future stroke
SC Johnston et al: Validation and refinement of score to predict very early stroke risk after transient ischaemic attack.
Lancet 369:283, 2007.

10. Risk factors for stroke (cont.)
Heart disease — Heart
disease, including atrial
fibrillation, valvular disease,
recent myocardial infarction,
and endocarditis, increases
the probability of a stroke
due to embolism. Of these,
atrial fibrillation is the most
prominent, causing nearly
half of all cardioembolic
strokes.
Wolf et al. 1991. Stroke. 1991; 22: 983-988

11. Risk factors for stroke (cont.)
 Hypertension — Hypertension is an
important stroke risk factor, including
isolated systolic hypertension.
Epidemiologic studies show that
there is a gradually increasing
incidence of both coronary disease
and stroke as the blood pressure
rises above 110/75 mmHg. Both
prior blood pressure and current
blood pressure are important risk
factors (for both ischemic and
hemorrhagic stroke).
Data from Prospective Studies Collaboration, Lancet 2002; 360:1903.

12. Risk factors for stroke (cont.)
JAMA. 2002;287(8):1003-1010.
10 years 15 years 20 years 25 years
Men 56% 78% 88% 93%
Women 52% 72% 83% 91%
0%
20%
40%
60%
80%
100%
%
Residual lifetime risk for developing
hypertension

13. Risk factors for stroke (cont.)
Stroke. 2015;46:1595-1600

14. Risk factors for stroke (cont.)
Bishop T, Figueredo VM. Hypertensive therapy: attacking the renin-angiotensin system. Western Journal of Medicine. 2001;175(2):119-124.

15. Stroke. 2014;45:3754-3832

16. Physical inactivity
Stroke. 2014;45:3754–3832.
• Physical activity is recommended because it is
associated with a reduction in the risk of stroke (Class I;
Level of Evidence B).
• Healthy adults should perform at least moderate- to
vigorous-intensity aerobic physical activity at least 40
min/d 3 to 4 d/wk (Class I; Level of Evidence B).

17. Diet
Stroke. 2014;45:3754–3832.
• Reduced intake of sodium and increased intake of potassium as
indicated in the US Dietary Guidelines for Americans are
recommended to lower BP (Class I; Level of Evidence A).
• A DASH-style diet, which emphasizes fruits, vegetables, and low-fat
dairy products and reduced saturated fat, is recommended to lower
BP (Class I; Level of Evidence A).
• A Mediterranean diet supplemented with nuts may be considered in
lowering the risk of stroke (Class IIa; Level of Evidence B).

18. Diet

19. Diet

20. Dyslipidemia
Stroke. 2014;45:3754–3832.
• In addition to therapeutic lifestyle changes, treatment
with an HMG coenzyme-A reductase inhibitor (statin)
medication is recommended for the primary prevention
of ischemic stroke in patients estimated to have a high
10-year risk for cardiovascular events as recommended
in the 2013 “ACC/AHA Guideline on the Treatment of
Blood Cholesterol to Reduce Atherosclerotic
Cardiovascular Risk in Adults” (Class I; Level of
Evidence A).

21. Dyslipidemia (cont.)
http://tools.acc.org/ASCVD-Risk-Estimator/

22. The Anglo-Scandinavian Cardiac Outcomes
Trial (ASCOT)
Sever PS et al. Lancet. 2003;361:1149-1158.

23. ASCOT LLA Secondary End Point: Fatal
and Nonfatal Stroke
23Sever PS et al. Lancet. 2003;361:1149-1158.
27% relative risk
reduction
HR = 0.73 (0.56 – 0.96) P = .0236
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5
0
1
2
3
Years
CumulativeIncidence,%
Atorvastatin 10 mg
Placebo
Number of Events 89
Number of Events 121

24. The HOPE-3 Trial
Argentina, Australia, Brazil, Canada, China, Colombia, Czech
Republic, Ecuador, Hungary, India, Israel, Korea, Malaysia,
Netherlands, Philippines, Russia, Slovakia, South Africa, Sweden,
United Kingdom, Ukraine
Global Trial: 228 centers in 21 countries

25. Intermediate-Risk Population
Inclusion Criteria (Target Risk 1.0%/yr)
Women ≥ 60 yrs, men ≥ 55 yrs with at least one additional
Risk Factor
• Increased WHR • Dysglycemia
• Smoking • Mild renal dysfunction
• Low HDL • Family history of CHD
Exclusion Criteria:
CVD or indication(s) or contraindication(s) to study drugs
No strict BP or LDL-C criteria for entry
Uncertainty principle

26. Rosuvastatin
Cand+HCTZ
n = 3,180
HOPE-3:
2 by 2 Factorial Design
14,682 Entered Single-blind 4 week Active Run-in
12,705 (87%) Randomized
Rosuvastatin
10 mg
n=6,361
Candesartan 16 mg +
HCTZ 12.5 mg
n= 6,356
Placebo
n = 6,349
Rosuvastatin
n = 3,181
Placebo
n = 6,344
Cand+HCTZ
n = 3,176
Double Placebo
n = 3,168
Simple follow-up and few blood tests
Median follow up = 5.6 years

27. Dyslipidemia (cont.)
N Engl J Med 2016;374:2021-31

28. Dyslipidemia (cont.)
N Engl J Med 2008;359:2195207.

31. Hypertension
Stroke. 2014;45:3754–3832.
• Annual screening for high BP and health-
promoting lifestyle modification are
recommended for patients with prehypertension
(SBP of 120 to 139 mmHg or DBP of 80 to 89
mmHg) (Class I; Level of Evidence A).
• Patients who have hypertension should be
treated with antihypertensive drugs to a target
BP of <140/90 mm Hg (Class I; Level of
Evidence A).

32. Hypertension (cont.)
Neurology® 2014;82:1153–1161

33. Hypertension
Stroke. 2014;45:3754–3832.
• J curve phenomenon

34. SPRINT trial
The SPRINT Research Group N Engl J Med 2015; 373:2103-2116
9361 persons was randomly assigned were at least 50 years old with a
systolic blood pressure of 130 mm Hg or higher (180 mmHg) and an
increased cardiovascular risk, but without diabetes, to a systolic blood-
pressure target of less than 120 mm Hg (intensive treatment) or a target of
less than 140 mm Hg (standard treatment).

35. SPRINT trial (cont.)
The SPRINT Research Group N Engl J Med 2015; 373:2103-2116
All participants had at least 1 other significant cardiovascular
risk factor, including chronic kidney disease; age 75 years or
older; a previous cardiovascular event (except stroke); or an
elevated cardiovascular risk based on their Framingham risk
score.

36. SPRINT trial (cont.)
The SPRINT Research Group N Engl J Med 2015; 373:2103-2116
The primary composite outcome was myocardial infarction,
other acute coronary syndromes, stroke, heart failure, or death
from cardiovascular causes. (Funded by the National Institutes
of Health; ClinicalTrials.gov

38. The intervention was stopped early after a median
follow-up of 3.26 years in stead of December
2018 which was the Estimated Study Completion
Date1
1- ClinicalTrials.gov. Systolic Blood Pressure Intervention Trial (SPRINT).
https://clinicaltrials.gov/ct2/show/NCT01206062?term=Systolic+Blood+Pressure+Intervention+Trial&rank=1. Accessed November 9,
2015.

39. SPRINT trial (cont.)

40. SPRINT trial (cont.)

41. SPRINT trial (cont.)

42. SPRINT trial (cont.)
The SPRINT Research Group N Engl J Med 2015; 373:2103-2116
Rates of serious adverse events of hypotension,
syncope, electrolyte abnormalities, and acute
kidney injury or failure, but not of injurious falls,
were higher in the intensive-treatment group than in
the standard-treatment group.

43. SPRINT trial (cont.)
Dr Marc Pfeffer (Harvard Medical School, Boston, MA)
CAUTIONS AS REGARD STUDY
A lot of effort is required to hit this target, including initial combination therapy
and frequent office visits “marathon effort”.
Excluding diabetics is "a black hole" in the study and limits its applicability.
Only approximately half of adults achieve a blood pressure of 140 mm Hg or
less, as consistent with current recommendations.
“Physicians "shouldn't expect a 'thank you' from patients
when you add another pill to reduce their blood pressure.“1

45. BP Lowering vs. Placebo:
SBP Changes
Years
SystolicBloodPressure(mmHg)
0 1 2 3 4 5 6 7
120125130135140
6356 5907 5667 5446 5213 3862 1437 350
6347 5879 5623 5442 5186 3822 1424 334
Cand/HCTZ
Placebo
Placebo
Candesartan/HCTZ
Δ BP=6.0/3.0 mmHg

46. BP Lowering vs. Placebo
Outcome
Cand+HCTZ
N=6356
Placebo
N=6349
HR
(95% CI)
p
Co-Primary 1 260 (4.1%) 279 (4.4%) 0.93 (0.79-1.10) 0.40
Co-Primary 2 312 (4.9%) 328 (5.2%) 0.95 (0.81-1.11) 0.51
Secondary 335 (5.3%) 364 (5.7%) 0.92 (0.79-1.06) 0.26
CV Death 155 (2.4%) 170 (2.7%) 0.91 (0.73-1.13) 0.40
MI 52 (0.8%) 62 (1.0%) 0.84 (0.58-1.21) 0.34
Stroke 75 (1.2%) 94 (1.5%) 0.80 (0.59-1.08) 0.14
CV Hosp. 319 (5.0%) 331 (5.2%) 0.96 (0.83-1.12) 0.63

47. BP Lowering vs. Placebo
N Engl J Med 2016;374:2009-20

48. BP Lowering vs. Placebo
N Engl J Med 2016;374:2009-20

49. BP Lowering vs. Placebo
N Engl J Med 2016;374:2009-20
• Learnt lessons from hypertension arm:
I. Blood pressure lowering doesn’t affect
CVD outcome in normtensive individuals
II. Blood pressure lowering affect CVD
outcome in hypertensive individuals

50. Risk factors for stroke (cont.)
Stroke. 2015;46:1595-1600

51. Obesity
Stroke. 2014;45:3754–3832.
• Among overweight (BMI=25 to 29 kg/m2) and obese
(BMI >30 kg/m2) individuals, weight reduction is
recommended for lowering BP (Class I; Level of
Evidence A).
• Among overweight (BMI=25 to 29 kg/m2) and obese
(BMI >30 kg/m2) individuals, weight reduction is
recommended for reducing the risk of stroke (Class I;
Level of Evidence B).

52. Obesity
Arch Intern Med. 2002;162:2557-2562

53. Stroke. 2011;42:30-36
Obesity paradox
One-month survival of patients after
acute first-ever stroke according to
body mass index.

54. Obesity paradox
Stroke. 2011;42:30-36
Long-term survival of patients after
acute first-ever stroke according to
body mass index.

55. Obesity Paradox (cont.)
Neurology 2016;87:1473–1481
Reverse Epidemiology

56. Obesity Paradox (cont.)
Neurology 2016;87:1–2
BMI is a crude measure of obesity and does not take into account fitness,
nutritional status, or body fat distribution.

57. Diabetes mellitus
Stroke. 2014;45:3754–3832.
• Control of BP in accordance with an AHA/ACC/CDC
Advisory to a target of <140/90 mmHg is recommended
in patients with type 1 or type 2 diabetes mellitus (Class
I; Level of Evidence A).
• The usefulness of aspirin for primary stroke prevention
for patients with diabetes mellitus but low 10-year risk of
CVD is unclear (Class IIb; Level of Evidence B).

58. Diabetes mellitus
Platelets, August 2011; 22(5): 338–344

59. Diabetes mellitus
Cardiovasc Diabetol. 2011;10:25.

60. Smoking
Stroke. 2014;45:3754–3832.
• Abstention from cigarette smoking is recommended

61. Lancet. 2016 Aug 20. 388 (10046):761-75

62. Atrial fibrillation
CHADS2 and CHA2DS2 VASc

63. Atrial fibrillation(cont.)
CHADS2 and CHA2DS2 VASc

64. Atrial fibrillation(cont.)
CHADS2 and CHA2DS2 VASc

65. Therapeutic
range
1
International normalized ratio
Oddsratio
2
15
8
10
5
0
1
3 4 5 6 7
20
71
VKAs have a narrow therapeutic window
ACC/AHA/ESC guidelines: Fuster V et al. Circulation 2006;114:e257–354
& Eur Heart J 2006;27:1979–2030
Stroke
Intracranial bleed
VKAs = vitamin K antagonists
Graphreproducedwithpermission:©2010AmericanCollegeofChestPhysicians

66. Primary Prevention (cont.)
HAS BLED score
HAS-BLED categorizes those into low (score 0-2) or high (≥3) risk, where the
latter can be identified for more regular review and follow-up.

67. Primary Prevention (cont.)
SAMe-TT2R2 Score
b= Two of the following: hypertension, diabetes mellitus, coronary artery disease
or myocardial infarctions, peripheral artery disease, congestive heart failure,
previous stroke, pulmonary disease, or hepatic or renal disease.

68. Atrial fibrillation(cont.)
SAMe-TT2R2 Score
 The SAMe-TT2R2 score is proposed as a means to help with decision making,
to identify those newly diagnosed nonanticoagulated AF patients who have a
probability of doing well while taking a vitamin K antagonist (VKA) (with SAMe-
TT 2R2 score, 0-2) and achieve a time in therapeutic range (TTR) of at least
65% or 70%.
 In contrast, a SAMe-TT2R2 score of more than 2 suggests that such patients
are unlikely to achieve a good TTR while taking a VKA, and a non-VKA oral
anticoagulant should be used upfront, without a “trial of warfarin” period.

69. Phase III RE-LY®: time to first stroke or systemic embolism
BID = twice daily; NI = non-inferiority; RR = relative risk; RRR = relative risk reduction; Sup = superiority
Years
0.0 0.5 1.0 1.5 2.0 2.5
0.01
0.02
0.03
0.05
0.04
Cumulativehazardrates
0.00
Warfarin
Dabigatran 110 mg BID
Dabigatran 150 mg BID
RR 0.90
(95% CI: 0.74–1.10)
P<0.001 (NI)
P=0.30 (Sup)
RR 0.65
(95% CI: 0.52–0.81)
P<0.001 (NI)
P<0.001 (Sup)
RRR
35%
Disclaimer: Dabigatran etexilate is not approved for clinical use in stroke prevention in atrial fibrillation outside the US and Canada.
This information is provided for medical education purposes only.
Please be aware that there may be national differences between countries regarding specific medical information,
including licensed uses, so please check local prescribing information for further details.
Connolly SJ et al. N Engl J Med 2010;363:1875–6

70. Phase III RE-LY®: haemorrhagic stroke
Connolly SJ et al. N Engl J Med 2009;361:1139–51; Connolly SJ et al. N Engl J Med 2010;363:1875–6
BID = twice daily; RR = relative risk; RRR = relative risk reduction; Sup = superiority
Haemorrhagicstroke(no.ofevents)
n: 6015 6076 6022
Dabigatran
110 mg BID
Dabigatran
150 mg BID
Warfarin
0
10
20
30
40
50
14
0.12% 12
0.10%
45
0.38%
RR 0.31 (95% CI: 0.17–0.56)
P<0.001 (Sup)
RR 0.26 (95% CI: 0.14–0.49)
P<0.001 (Sup)
RRR
69%
RRR
74%
Disclaimer: Dabigatran etexilate is not approved for clinical use in stroke prevention in atrial fibrillation outside the US and Canada.
This information is provided for medical education purposes only.
Please be aware that there may be national differences between countries regarding specific medical information,
including licensed uses, so please check local prescribing information for further details.

71. Phase III AVERROES: stroke or systemic
embolic event
Connolly SJ et al. Presented at ESC 2010; session number 708005-708006.
Available at: http://www.escardio.org/congresses/esc-2010/congress-
reports/Pages/708-3-AVERROES.aspx [Accessed September 2010]
RR = relative risk; CI = confidence interval
Cumulativerisk
0.02
0.04
0.05
0.06
0.07
0
0.01
0.03
0
Months
3 6 9 12 18 21
2791 2720 2541 2124 1541 626 329
2809 2761 2587 2127 1523 617 352
Aspirin
Apixaban
RR 0.46
95% CI: 0.33–0.64
P<0.001
Aspirin
Apixaban

72. Other Cardiac conditions
Stroke. 2014;45:3754–3832.
• Anticoagulation is indicated in patients with mitral
stenosis and a prior embolic event, even in sinus rhythm
(Class I; Level of Evidence B).
• Vitamin K antagonist therapy is reasonable for
patients with STEMI and asymptomatic left ventricular
mural thrombi (Class IIa; Level of Evidence C).
• Anticoagulant therapy may be considered for
patients with STEMI and anterior apical akinesis or
dyskinesis (Class IIb; Level of Evidence C).

73. Asymptomatic Carotid stenosis
Stroke. 2014;45:3754–3832.
• It is reasonable to repeat duplex ultrasonography annually to assess
the progression or regression of disease and response to therapeutic
interventions in patients with atherosclerotic stenosis >50% (Class
IIa; Level of Evidence C).
• Patients with asymptomatic carotid stenosis should be prescribed
daily aspirin and a statin. (Class I; Level of Evidence C).
• It is reasonable to consider performing CEA in asymptomatic patients
who have >70% stenosis of the internal carotid artery if the risk of
perioperative stroke, MI, and death is low (<3%). However, its
effectiveness compared with contemporary best medical management
alone is not well established (Class IIa; Level of Evidence A).

74. Aspirin for primary prevention
Stroke. 2014;45:3754–3832.
• The use of aspirin for cardiovascular (including but not specific to
stroke) prophylaxis is reasonable for people whose risk is sufficiently
high (10-y risk >10%) for the benefits to outweigh the risks
associated with treatment.
(Class IIa; Level of Evidence A).
• Aspirin is not useful for preventing a first stroke in low-risk
individuals (Class III; Level of Evidence A).
• Aspirin is not useful for preventing a first stroke in people with
diabetes mellitus in the absence of other high-risk conditions (Class
III; Level of Evidence A).

75. N Engl J Med 2016;374:2032-43.

76. Rosuva +
Cand+HCTZ
n = 3,180
HOPE-3:
2 by 2 Factorial Design
N = 12,705
Rosuva
10 mg
n=6,361
Cand 16 mg+
HCTZ 12.5 mg
n= 6,356
Placebo
n = 6,349
Rosuva
n = 3,181
Placebo
n = 6,344
Cand+HCTZ
n = 3,176
Double
Placebo
n = 3,168

77. Polypill concept revisited
Candesartan + HCZ + Rosuvastatin
N Engl J Med 2016;374:2032-43.

78. Combination vs Double Placebo:
Change in SBP and LDL-C
0 Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7
120125130135140
Week 6
Combination
Cand + HTCZ
Rosuva
Double placebo
SBP
Month 6
0 Year 1 Year 3 Study End
8090100120140
Combination
Rosuva
Cand + HCTZ
Double placebo
LDL-C
Combination
Rosuva.
Double Placebo
Cand+HCTZ
Mean Δ 6.2 mmHg
Mean Δ 33.7 mg/dl

79. Combination vs Double
Placebo
Outcome
Double Active
N=3,180
N (%)
Double Placebo
N=3,168
N (%)
HR
(95% CI)
p
Co-Primary 1 113 (3.6) 157 (5.0) 0.71 (0.56, 0.90) 0.0054
Co-Primary 2 136 (4.3) 187 (5.9) 0.72 (0.57, 0.89) 0.0030
Secondary 1 147 (4.6) 205 (6.5) 0.71 (0.57, 0.87) 0.0012
CV Death 75 (2.4) 91 (2.9) 0.82 (0.60-1.11) 0.19
MI 21 (0.7) 31 (1.0) 0.55 (0.32-0.93) 0.026
Stroke 31 (1.0) 44 (1.4) 0.56 (0.36-0.87) 0.009
CV Hosp 141(4.4) 191 (6.0) 0.73(0.59-0.91) 0.0046

80. CV Death, MI, Stroke,
Cardiac Arrest, Revasc, Heart Failure
Years
CumulativeHazardRates
0.00.020.040.060.080.10
0 1 2 3 4 5 6 7
Rosuvastatin
Cand + HCTZ
Combination
Double Placebo
HR (95% CI) = 0.72 (0.57-0.89)
P-value = 0.0030
3180 4 3063 1057
3181 3061 1045
3176 3040 1019
3168 3035 1030
Combination
Rosuvastatin
Candesartan/HCTZ
Double Placebo

81. Coronary Heart Disease Stroke
Coronary Heart Disease: Fatal/non-fatal MI, Coronary Revascularization
Years
CumulativeHazardRates
0.00.010.020.030.040.05
0 1 2 3 4 5 6 7
CombinationRosuvastatin only
Candesartan/HCTZ onlyDouble Placebo
Years
0.00.0050.0100.0150.0200.025 0 1 2 3 4 5 6 7
HR (95% CI) = 0.62 (0.43-0.88)
P-value = 0.0085
HR (95% CI) = 0.56 (0.36-0.87)
P-value = 0.0094

82. Combination vs
Double Placebo: Safety
Combination
N=3,180
N (%)
Double Placebo
N=3,168
N (%)
Permanent Discontinuation of Both 697 (21.9) 757 (23.9)
Rhabdomyolysis/Myopathy of Rosuva 1 (0) 1 (0)
Muscle pain/ weakness 196 (6.2) 131 (4.1)
Lightheadedness (BP Only) 48 (1.5) 40 (1.3)
Renal Dysfunction/Potassium Abn. 6 (0.2) 6 (0.2)
New Diabetes 123 (4.1) 113 (3.8)
Cataract Surgery 84 (2.8) 88 (2.9)

83. Combination vs
Double Placebo: Conclusions
• About a 30% reduction in major vascular
events
• Benefits of combination therapy:
– Largely seen in those in the upper third of
SBP (40% RRR in CVD)
– In lower two thirds the benefit is from
Rosuvastatin only (30% RRR in CVD)

84. Clinical Implications
• Statins beneficial in all participants
• BP lowering benefits only those with elevated BP
• Combination therapy:
– In hypertensives, leads to a 40% risk reduction
(benefits from both BP lowering and statin)
– In others, 30% RRR from statin alone

87. Franklin D. Roosevelt
President of US from 1933 until his death
in 1945
Died: April 12, 1945 (aged 63)
Famous People Who Died of Stroke
http://www.ranker.com/list/famous-people-who-died-of-stroke/reference

88. Howard G. Bruenn, "Clinical Notes On The Illness and Death of President Franklin D. Roosevelt," Ann. of Int. Med. 72 (1970): 579–59.
Franklin Delano Roosevelt:
represents a unique and superb
example of the natural history of
untreated hypertension and the
complications that can arise if left
untreated.
Dr Bruenn reported the President's
last words: "I have a terrific
headache.“
Of notable FDR had suffered also
from severe anemia (Hb: 4.5 gm%),
proteinuria 4+ and cholelithiasis!!!

89. Risk factors for stroke (cont.)
Bishop T, Figueredo VM. Hypertensive therapy: attacking the renin-angiotensin system. Western Journal of Medicine. 2001;175(2):119-124.

90. Joseph Stalin
The leader of the Soviet Union from the
mid-1920s until his death in 1953
Died: 5 March 1953 (aged 74)
Famous People Who Died of Stroke
http://www.ranker.com/list/famous-people-who-died-of-stroke/reference

91. Sir Winston Churchill
Prime Minister of the United Kingdom from
1940 to 1945 and again from 1951 to 1955
Died: 24 January 1965 (aged 90)
Famous People Who Died of Stroke
http://www.ranker.com/list/famous-people-who-died-of-stroke/reference

93. Overall Bottom Line
Remember
• Prevention of risk is better than treating it.
• Exercise a lot.
• Stop smoking even before you start it.
• Lipid and BP leads to harmful consequences treat them
first.

94. Thanks