1. Hypertension Around the World: Strategies for Controlling Hypertension in Challenging Situations
George Bakris, MD, F.A.S.N., FA.H.A., F.A.S.H.
Professor of Medicine
Director, ASH Comprehensive Hypertension Center
University of Chicago Medicine
Chicago, IL

2. What is hypertension and how is it different from high blood pressure
Hypertension is a genetically predisposed sustained elevation in blood pressure that occurs usually between the 3rd-6th decade of life and not associated with a correctable hemodynamic or endocrine cause.
Elevated blood pressure is a periodic increase in pressure related to excess stress and resolves with relaxation or rest

3. High Blood Pressure in the United States
Having high blood pressure puts you at risk for heart disease and stroke, which are leading causes of death in the United States.
About 75 million American adults (32%) have high blood pressure—that’s 1 in every 3 adults.
About 1 in 3 American adults has prehypertension—blood pressure numbers that are higher than normal—but not yet in the high blood pressure range.
Only about half (54%) of people with high blood pressure have their condition under control.
High blood pressure was a primary or contributing cause of death for more than 410,000 Americans in 2014—that's more than 1,100 deaths each day.
High blood pressure costs the nation $48.6 billion each year. This total includes the cost of health care services, medications to treat high blood pressure, and missed days of work.

5. Prevalence of Hypertension by Gender, Race, and Survey U.S.: 1988-2006
The prevalence of hypertension (blood pressure [BP] ≥140/90 mm Hg, or taking antihypertensive medicine) rises with increasing age. Fifty million Americans, or 1 in 4 adults, has hypertension.
A greater percentage of men than women have high BP until age 55 years.
The prevalence of hypertension among blacks in the US is among the highest in the world. Compared with whites, blacks develop hypertension earlier in life, and their mean BPs are much higher. As a result, compared with whites, blacks have a 1.3x greater rate of nonfatal stroke, a 1.8x greater rate of fatal stroke, a 1.5x greater rate of heart disease death, and a 4.2x greater rate of end-stage renal disease.
As many as 30% of all deaths in hypertensive black men and 20% of all deaths in hypertensive black women may be due to hypertension.
The estimated direct plus indirect costs for hypertension in the US for 2003 is over $50 billion.
References
Wolz M, Cutler J, Roccella EJ, et al. Statement from the National High Blood Pressure Education Program: prevalence of hypertension. Am J Hypertens. 2000;13:
American Heart Association. Heart Disease and Stroke Statistics Update. Dallas, TX: American Heart Association; 2002.
Adapted from: Lloyd-Jones D, et al. Heart Disease and Stroke Statistics – 2009 Update. Circulation. 2009;119:e1-161.

6. Awareness, Treatment, and Control Rates by Race/Ethnicity
NHANES 2003–2004 %
Reference
Ong KL, Cheung BMY, Man YB, Lau CP, Lam KSL. Prevalence, awareness, treatment, and control of hypertension among United States adults 1999–2004. Hypertension. 2007;49:69–75.
Age adjusted.
NHANES=National Health and Nutrition Examination Survey; hypertension=average BP ≥140/90 mm Hg, or patient was taking antihypertensive medications.
Ong KL et al. Hypertension. 2007;49:69-75.

7. Prevalence, Awareness, Treatment, for 1988–1994 & and Control 1999–2008
Egan B et.al. JAMA 2010;303:

8. Global Burden of Hypertension* 2025 Projection
Year 2000
26.4% of world adult population had hypertension
Total of 972 million adults
Highest prevalence is in established market economies (eg, North America, Europe)
Year 2025
29.2% of world adult population will have hypertension
Total of 1.56 billion adults (60%  overall; 24%  in developed nations, 80%  in developing nations)
Highest prevalence will be in economically developing continents (e.g., Asia, Africa) will account for 75% of world’s hypertensive patients
*As defined by a blood pressure >140/90 mm Hg; >130/80 mm Hg in diabetes and renal impairment
Kearney PM et al. Lancet. 2005;365:

9. Does Hypertension Cause ESRD?

10. Age-Adjusted Rate of ESRD
HTN Linked To Chronic Renal Disease Among 332,544 Men Screened for MRFIT
<80
80-84
85-89
90-99
110
Age-Adjusted Rate of ESRD
Per 100,000 Person-Years
180
<120
Systolic BP (mm Hg)
Diastolic BP (mm Hg)
HTN Linked to Chronic Renal Disease Among 332, 544 Men Screened for MRFIT
Talking Points: In this slide, age-adjusted rates of ESRD due to any cause per 100,000 person-years have been plotted against systolic and diastolic blood pressure in the 332,544 men screened for the Multiple Risk Factor Intervention Trial (MRFIT) from 1973 to Data on men with stage 3 and stage 4 hypertension were combined because of their smaller numbers. Higher blood pressure, as measured carefully on a single occasion, was a strong independent risk factor for end stage renal disease. The increase in risk associated with higher blood pressure was graded and continuous throughout the distribution of blood‑pressure readings above the optimal level. Risk estimates for ESRD were graded for both systolic and diastolic blood pressure considered separately, but systolic pressure was the stronger predictor of subsequent disease when both variables were considered together.
References: Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Ford CE et al. Blood pressure and end-stage renal disease in men. N Engl J Med 1996;334(1):13-18.
Keywords: Blood Pressure, Hypertension, Incidence, Renal Failure, Epidemiology, Male
Klag, MJ et al NEJM 1996;334:13-18

11. 17 Year Follow-Up from VA Hypertension Clinics on ESRD
H. M. Perry, Jr., et.al Early predictors of 15-year end-stage renal disease
in hypertensive patients. Hypertension 25 (4 Pt 1): , 1995.

12. Hypertension: The 2nd Most Common Cause of ESRD
Primary Diagnosis For Patients Who Start Dialysis
Diabetes
50.1%
Hypertension
27%
Glomerulonephritis
13%
Other
10%
No of Patients
Projection
95% CI
700
600
500
Number of
Dialysis
Patients
400
Slide I-14
The pie chart shows that diabetes is currently the most common cause of ESRD.
The lower graph reveals that the number of patients with ESRD maintained on dialysis is predicted to double over present levels by 2010, and the major contributor to this exponential increase is chronic renal failure associated with diabetes.
United States Renal Data System. Annual data report [Accessed on 25 April 2001] Available at URL:
300
520,240
281,355
200
243,524
100
R2 = 99.8%
1984
1986
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
United States Renal Data System. Annual data report

13. Risk of coronary events in people with CKD compared with diabetes: a population-level cohort study
NHANES 2003−2006
48-month follow-up
N=1,268,029
Tonelli M et al. Lancet 2012;380:807

14. Prevalence, Awareness, Treatment, and Control of Hypertension in Total KEEP Cohort by CKD stage with140/90 mm Hg as threshold. (N=10,819) %
Sarafidis P et.al. Am J Med 2008;121:

15. Key points to achieve success with BP goal
Need patient buy-in-best way is to educate as to disease and consequences with data
Need to see patient more frequently in beginning and encourage communication in the interim-Send a signal you care and disease is important

16. Patient Factors of Compliance
Influences on compliance involve
The patient, the disorder, the treatment, and the therapeutic environment
Study: Why patients discontinue treatment
11% due to undesirable side effects
25% thought their doctor told them to
46% thought they were cured
6% due to cost
Improving issues of compliance requires a multipronged approach
Factors influencing compliance include the patient, the disorder, the treatment and the therapeutic environment. Gallup showed that 11% of patients treated with an antihypertensive stopped their treatment because of undesirable side effects, 25% because they though that their doctor had asked them to, 46% because they thought they had been cured and 6% for financial reasons.
In an effort to reduce BP in the general population, the American Public Health Association and the NHBPEP Coordinating Committee recently recommended that the food industry, including manufacturers and restaurants, reduce sodium in the food supply by 50% over the next decade.
Reference(s)
Mallion JM, Schmitt D. Patient compliance in the treatment of arterial hypertension. J Hypertens Dec;19(12):
Gallup G Jr, Cotugno HE. Preferences and practices of Americans and their physicians in antihypertensive therapy. Am J Med. 1986; 81(suppl 6c): 20-4.
Whelton PK, He J, Appel LJ, Cutler JA, Havas S, Kotchen TA, et al. Primary prevention of hypertension: Clinical and public health advisory from The National High Blood Pressure Education Program. JAMA. 2002;288:
Mallion JM, Schmitt D. J Hypertens Dec;19(12):
Gallup G Jr, Cotugno HE. Am J Med. 1986; 81(suppl 6c):
Whelton PK, et al. JAMA. 2002;288:

17. Barriers to Achieving Goal Blood Pressure
Cultural norms
Insufficient attention to health education by health care practitioners
Lack of reimbursement for health education
Lack of access to places for physical activity
Larger servings of food in restaurants
Lack of availability of healthy food choices in many schools, worksites, and restaurants
Lack of exercise programs in schools
Large amounts of sodium added to foods by the food industry and restaurants
Higher cost of food products that are lower in sodium and calories
Several barrier to achieving goal BP exist and include cultural norms; insufficient attention to health education by health care practitioners; lack of reimbursement for health education services; lack of access to places to engage in physical activity; larger servings of food in restaurants; lack of availability of healthy food choices in many schools, worksites, and restaurants; lack of exercise programs in schools; large amounts of sodium added to foods by the food industry and restaurants; and the higher cost of food products that are lower in sodium and calories. Overcoming the barriers will require a multipronged approach directed not only to high-risk populations, but also to communities, schools, worksites, and the food industry.
Reference(s)
Whelton PK, He J, Appel LJ, Cutler JA, Havas S, Kotchen TA, et al. Primary prevention of hypertension: Clinical and public health advisory from The National High Blood Pressure Education Program. JAMA. 2002;288:
Whelton PK, et al. JAMA. 2002;288:

18. AHA BP Measurement Recommendations 2005
Recommendations for Blood Pressure Measurement in Humans and Experimental Animals
Part 1: Blood Pressure Measurement in Humans: A Statement for Professionals From the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research
Hypertension 2005;45: Note: 19 pages!

19. Modified from Bruce et al, Observer bias in blood pressure studies.
Systolic BP Differences Between Research Nurses During a 24 Month Study: Effect of Training (T). -5 5 10 15
Nurse 1
Nurse 2 12 T
Nurse 4
Nurse 3
-10
Month of Study
Difference
21 mm Hg!
Systolic
Difference
from
Group
Mean
(mm Hg)
Difference
0 mm Hg!
Modified from Bruce et al, Observer bias in blood pressure studies.
J. Hypertension 1988; 6:

20. BP Recommendations:
Multiple readings are needed for classification and to guide treatment.
Automated devices can take multiple readings but accuracy must be validated on each patient before they can be relied upon for individual accuracy.
Home BP readings predict risk better than office.
24 hour BP measurements MAY be better at predicting risk.
Failure of BP to decline during sleep increases risk.
In obese adults and children appropriate cull selection is of paramount importance.

21. NY Times: What’s wrong with this picture?
Noisy
Fan?
Room
too
cold?
Ear Pieces in wrong?
Watching
Manometer
Stetho head
at center
of arm
Eyes closed?
Not at
eye
level
Using
Diaphragm
Cuff over
Clothes
+10/+5
Tubing
flopping
Stetho
too long.
Observer’s
Arms not
Resting on
Table
Cuff above
Heart Level
+2 mm / inch
No Back
Support
+10/+6
Lg Cuff?
Manometer
too far away
Legs Crossed
+10/+5
Arm not
supported
Left arm
100 mm Hg

22. Difference Between Office and Trial BP readings
Routine Office BP measurements
“automated office BP” (AOBP). Like the SPRINT method, AOBP measurement assesses BP after the patient has rested for 5 minutes, but adding to that a fully automated sequence of 5 readings over a 5-minute period, all with the patient resting quietly alone4.
AOBP method corresponds more closely with mean daytime ambulatory BP (using ambulatory-awake monitoring)
BP recorded in research studies using the standard BP measurement guidelines, which mandate a rest period prior to measurement (with or without AOBP), is on average 10/7 mmHg lower than BP measured in routine clinical practice.
Bakris G Circulation, Sept 2016

23. Lifestyle Modification
Approximate SBP reduction (range)
Weight reduction
5-20 mm Hg/10-kg weight loss
Adopt DASH eating plan
8-14 mm Hg
Dietary sodium reduction
2-8 mm Hg
Physical activity
4-9 mm Hg
Lifestyle modifications reduce BP, prevent or delay the incidence of hypertension, enhance antihypertensive drug efficacy, and decrease cardiovascular risk. For example, in some individuals, a 1,600 mg sodium DASH eating plan has BP effects similar to single drug therapy. Combinations of two (or more) lifestyle modifications can achieve even better results. For overall cardiovascular risk reduction, patients should be strongly counseled to quit smoking.
Reference(s)
Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344:3-10.
Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer PJ, et al. Effects of comprehensive lifestyle modification on blood pressure control: Main results of the PREMIER clinical trial. Writing Group of the PREMIER Collaborative Research Group. JAMA. 2003;289:
Moderation of alcohol consumption
2-4 mm Hg
Chobanian A et.al. JNC 7 Hypertension Dec 2003.

24. SALT

25. The INTERSALT Study
Figure The INTERSALT Study [51] was undertaken to determine the relationship between urinary sodium excretion (which reflects dietary sodium intake) and blood pressure. Two hundred individuals were studied at each of 52 centers throughout the world. Averages for urinary sodium excretion (adjusted for age, sex, body mass index, and alcohol consumption) and blood pressure rise with age are shown. Each point represents one center. From the slope of the regression line ( ± mm Hg/y/mmoL Na+) the magnitude of the effect of urinary sodium excretion can be estimated; reduction of sodium intake by 100 mmoL/d could reduce the rise in systolic blood pressure by 3.4 mm Hg for a period of 10 years [51].
52 centers, averages for urinary Na+ excretion (reflects dietary Na+
intake) and blood pressure rise with age

26. DASH-Sodium Results High Na+ – 150 mmol/d (3.3 g/d)
Int Na+ – 100 mmol/d
(2.5 g/day)
Low Na+ – 50 mmol/d
(1.5 g/day)
DASH Diet effective at lowering BP
On Control Diet
High to Intermediate Salt Levels and Intermed to Low – All Significant Changes
DASH diet: Significant changes from high to intermed and intermed to low in systolic
Only significant for diastolic in intermed to low
Sacks FM et al. N Engl J Med 2001;344:6.

27. Relationship between Salt Intake and Deaths from Strokes in 12 European countries.
Perry IJ, Beevers DG. Salt intake and stroke: a possible direct effect. J Hum Hypertens 1992; 6: 23–25.; He FJ and MacGregor G. J Hum Hypertens 2009;23:

28. Facts About Salt Intake in US
Average daily consumption is about mg/day.
Recommendation is 2400 mg.
Patients, in general have no concept about their salt intake

29. Changes in salt intake as measured by 24 h urinary sodium excretion (UNa), blood pressure, stroke and ischemic heart disease (IHD) mortality in England from 2003 to 2011.
*p<0.05, ***p<0.001 for trend.
He FJ et.al. BMJ Open 2014;4:e doi: / bmjopen

30. 19 Year Survival Curve in Japan- The thick line indicates survival for the participants with the Reduced-Salt Japanese Diet
Thick line-Reduced-Salt Japanese Diet
Thin-line-Regular Japanese Diet
Nakamura et.al. Br J Nutrition (2009);101:1696–1705

31. Daily Recommended Intake - 1 teaspoon salt = 2,400 mg Sodium
1 teaspoon baking soda = 1000 mg sodium
1 teaspoon soy sauce = 1000 mg sodium

32. Common Food Sources Table Salt Cured meats – deli meats, sausages, ham
Baking soda- bicarbonate of soda
Baking powder
Antacids
Snack foods – salted nuts, chips, pretzels, crackers
Canned soups and bouillon cubes
Cheeses
Condiments – pickles, ketchup, mustard
Seasonings and flavor enhancers – MSG
Ethnic Foods – Asian-( Chinese, Japanese)

33. Saltiest Side Dishes 5. Saltiest Mexican Entrée
Chili's Buffalo Chicken Fajitas-5,690 mg sodium, 1,730 calories
4. Saltiest Kids' Meal
Così Kid's Pepperoni Pizza- 6,405 mg sodium, 1,901 calories
3. Saltiest Seafood Entrée
Romano's Macaroni Grill Grilled Teriyaki Salmon- 6,590 mg sodium, 1,230 calories,
2. Saltiest Appetizer
Papa John's Cheesesticks with Buffalo Sauce- 6,700 mg sodium, 2,605 calories,
1. The Saltiest Dish in America
Romano's Macaroni Grill Chicken Portobello-7,300 mg sodium, 1,020 calories, 66 g fat

34. The African-American Study of Kidney Disease and Hypertension
For The AASK Study Group Investigators
Wright JT Jr et.al. JAMA, 2002

35. Baseline Characteristics by Randomized Group
Blood Pressure Goal Intervention
Characteristic
Lower (n = 540)
Usual (n = 554)
Age, mean (SE), y
54.5 (10.9)
54.7 (10.4)
Female, No. (%)
205 (38.0)
219 (39.5)
Blood Pressure, mean (SE), mm Hg
Systolic
152 (25)
149 (23)
Diastolic
96 (15)
95 (14)
Mean arterial pressure
115 (17)
113 (15)
GFR, mean (SE) mL/min per 1.73 m2
46.0 (12.9)
45.3 (133.2)
Serum creatinine, mean (SE), mg/dL
Male
2.17 (0.75)
2.20 (0.77)
Female
1.72 (0.55)
1.81 (0.57)
Urine protein/creatinine ratio, mean (SE)
0.33 (0.50)
0.32 (0.52)
0.28 (0.48)
0.37 (0.58)
Urine protein, mean (SE), g/24 h
0.61 (1.01)
0.61 (1.08)
0.36 (0.63)
0.46 (0.81)
With urinary protein to creatinine ratio of at least 0.22, No. (%)
181 (33.5)
176 (31.8)

36. Mean Arterial Pressure During Follow-up80 90
100
110
120
130
Lower BP Goal (Achieved: 128/78)
Usual BP Goal (Achieved: 141/85)
MAP (mm Hg) 4 12 20 28 36 44 52 60
Follow-up Month
Wright JT Jr. et.al. JAMA 2002

37. Composite Clinical Events: Declining GFR Event,
ESRD or Death by BP Goal 40
Low (Achieved: 127/77) 35
Usual BP ((Achieved: 140/85) 30
Low vs. Usual:
RR=2%, (p=0.85) 25
% with Events 20 15 10 5 6 12 18 24 30 36 42 48 54 60
Follow-Up Time (Months)
RR=Risk Reduction
Wright JT Jr, et.al. JAMA, 2002

38. Composite Clinical Events: Declining GFR Event,
ESRD or Death by BP Goal
Baseline UP/Cr
0.22 70
Low (Achieved: 127/77)
Usual BP ((Achieved: 140/85) 60 50
Low vs. Usual:
RR= -31%, (p=0.11) 40
% with Events 30 20 10 6 12 18 24 30 36 42 48 54 60
Follow-Up Time (Months)
RR=Risk Reduction

39. Composite Clinical Events: Declining GFR Event,
ESRD or Death by BP Goal
Baseline UP/Cr>0.22 70
Low (Achieved: 127/77) 60
Usual BP ((Achieved: 140/85) 50
Low vs. Usual: 40
RR=17.8%, (p=0.18)
% with Events 30 20 10 6 12 18 24 30 36 42 48 54 60
Follow-Up Time (Months)
RR=Risk Reduction

40. Blood Pressure Control Throughout AASK Cohort Period

41. Appel L et al. Arch Intern Med 2008
Cumulative Incidence of Events (Doubling SCr, ESRD, or Death) 60
Only Trial
Mixed Trial and Cohort
Only Cohort
Composite 50 40
ESRD or Doubling SCr
Cumulative Incidence (%) 30 20 10
Death 1 2 3 4 5 6 7 8 9 10
Appel L et al. Arch Intern Med 2008
Follow-up Time (Years)
Number at Risk:
1094
1064
986
918
831
739
635
555
490
331
176

42. Comparison of clinic systolic BP (SBP) and nighttime ambulatory SBP
Pogue V, et.al Hypertension2009;53(1):20-7.

43. KNow the most effective affordable agents within the class
* P-values reported are Bonferroni adjusted

44. Certain generics have documented potency issues
Angiotensin receptor blockers-
Example-Losartan-well documented impurities create side effects not associated with drug-branded agent does fine.- pick another ARB-irbesartan tends to be much better.
Diuretics

45. Mean Office SBP Change Ernst ME, et al. Hypertension 2006; 47:352-358
Week 2
HCTZ : -4.5±2.1
Chlor : ±2.2
p=0.001*
Week 4
HCTZ : -7.6±2.8
Chlor : ±2.9
p=0.069*
Week 8
HCTZ : ±3.5
Chlor : ±3.7
p=0.842*
Week 6
HCTZ : -9.3±3.2
Chlor : ±3.4
p=0.109*
* P-values reported are Bonferroni adjusted
Ernst ME, et al. Hypertension 2006; 47:

46. Factors to ensure BP reduction and control among those with limited resources
Educate, which should lead to
Enpowerment, which should lead to
Enabling, which should lead to improved control