Managing Hypertension Beyond BP Control

Rajeev Gupta, MD PhD FACC

Fortis Escorts Hospital, Jaipur 302017 & Rajasthan University of Health Sciences, Jaipur 302023 India

Major Causes of Death in India: All Ages

Million Death Study 2001-2003
25

Analysis of cause of deaths in 1.1 million households and 113,692 persons in all the Indian States
20.3 16.9

20

CVDs caused 1.7-2.0 million deaths annually

Male Female

15

10

9.3 8 6.7

9.9 6.4 6.2 7.1 5.4 7.1 4.7 5.4 6

5.2

4.5

Cardiovascular

COPD

Diarrhea

Perinatal

Respiratory

TB

Cancers

Injuries

Million Death Study 2009

Cardiovascular Mortality in Different Indian States: Million Death Study

Males Females

Mony P, et al. 2009

https://tspace.library.utoronto.ca/bitstream/1807/18899/3/Mony_Prem%20kumar_200911_MSc_Thesis.pdf

Burden of Risk Factors

Major Population-wide Cardiovascular Risk Factors

WHO. Global Health Risks. 2009

Hypertension: A Major Cardiovascular Risk Factor

Kaplan & Opie. Lancet 2006; 367:168-176 Danaei G, et al. PLoS Med 2009; 6:e1000058

Risk Factors for AMI in South Asians

INTERHEART Study. Population Attributable Risks %
5 0 4 0 3 0 2 0 1 0 0
Di ab et es Hi gh W HR Ps yc ho so ci al Ap oB /A po A1 Sm ok in g Hy pe rte ns io n Ex er ci se
4 .85 6 4 .9 3 .56 7 3 .2 3 .7 7 3 .3 3 2 .9 3 1 .3 9 1 .82 1 1 .5 1 .6 9 1 .1 6 2 .4 7 2 .2 5 2 .4 1 1 .8 5 1 .2 2 Sout Asians h Ot hers

-1 0

-4 .6

Joshi PP, et al. JAMA 2007; 297:286-94

Fr ui ts /V eg

Al co ho l

Ten Risk Factors for Stroke

INTERSTROKE Study: Population Attributable Risk
7 .6 3

7 0 6 0 5 0 4 0 3 0 2 0 1 0 0
Sm ok ing Hi gh W HR Hy pe rte ns ion Di et ris k
2 .4 1 9 .5 4 .2 5 2 .1 6 2 .1 6 2 .6 7 9 2 .1 2 .4 4 1 .3 7 7 .9 1 .1 1 .6 4 3 .5 1 .1

Ischem ic Hem orrhage

3 .2 5

8 .5

Ph ys ica l Di ab et es Hi gh alc oh ol Ps yc ho

ODonnel M, et al. Lancet 2010; 376:112-23

Ca rd ia c Ap oA /A po B

Increasing Hypertension in India

Rural populations: BP >160/95
8 7

Percent Prevalence

6 5 4 3 2 1 0 1955 1.9 0.5 Delhi

r =0.19
2

7.1 5.6 5.4 3.6

Rajasthan

Rajasthan

Haryana 2.6
2.4

4.3 4.1 3.8 3.4 Haryana Maharashtra Chandigarh 2.6

Rajasthan
1.6

Maharashtra Orissa U.P.

0.4 0.3 1975 1985

Punjab
1995Himachal2005

1965

Bombay

U.P.

Orissa

Years Gupta R, et al. J Human Hypertens 1996; 10:465-472

Increasing Hypertension in India

Urban populations: BP >160/95
18 16 14 15.5 Bombay 14.1 Ludhiana 13.1 11.6 10.9 Delhi

Percent Prevalence

r2=0.70
9.2 Railways 6.4 4.2 1.2 1955 Calcutta 3.1 4.3

12 10 8 6 4 2 0 1945

Jaipur

Jaipur

Kanpur 1965 Bombay 1975 Agra 1985

Rohtak 1995

Years Gupta R, et al. J Hum Hypertension 1996;10:465-472

Recent Studies on Hypertension in India

Urban populations: BP >140/90
60 50

r2=0.37
41 33 29 34 31 45 44 42 38

Percent Prevalence

40 30 20 1993

Delhi
25

38 36

Mumbai

Jaipur Jaipur
2005 2007

Jaipur
1995 1997 1999 M en

Chennai
2001 W omen

Mumbai

2003

Gupta R. J Human Hypertens 2004; 18:73-78

Risk Factor Trends in Urban Rajasthan

Jaipur Heart Watch Studies 1992-2006

Gupta R, et al. Heart 2008; 94:16-26

Lifetime Risk of Hypertension

Framingham Heart Study

Vasan et al. JAMA 2002; 287:1003-10

Hypertension: The Neglected Disease of 21st Century Lancet 2009

.. Control of blood pressure is no longer disputed & is supported by most impressive evidence base medicine in past and even today

SBP Distribution & Mortality

Whelton PK et al. JAMA 2002; 288: 1882-8

Prospective Studies Collaboration. Lancet 2002

Cardiovascular Benefits of Reducing BP

Systolic BP
1 0.8 0.6 0.4 0.2 0 40-49 50-59 Stroke 60-69 IHD Vascular 70-79 80-89
0.49 0.36 0.43 0.5 0.38 0.5 0.54 0.53 0.43 0.5 0.6 0.64 0.67 0.67 0.7

Hazard ratio Diastolic BP

1 0.8 0.6 0.4 0.2 0 40-49 50-59
0.47 0.35 0.52 0.43 0.34

0.56 0.48 0.4

0.62 0.49 0.48

0.61

0.63

0.7

0.71

60-69 Stroke IHD Vascular

70-79

80-89

Reduction of usual systolic BP (upper panel) and diastolic BP (lower panel) is associated with a lower hazard ratios (hazard ratio <1.0) for mortality from stroke, ischemic heart disease (IHD) as well as other vascular causes.

Blood Pressure Goals & CVD Prevention

Goals:
Reduce and preserve normal blood pressure Increase rates of BP control

Promoters:
Physical activity, healthy diet, good medical care, medication, health insurance, diabetes control, weight loss. Healthy food environments, stable income and working conditions, health promotion and education

Barriers:
Physical inactivity, high salt high fat diet, obesity, diabetes, stress, lack of medical care, medication cost, tobacco use. Lack of access to medical care, medications, and recreation. Unemployment. Social stressors, social conflict.
Centers Disease Control, USA 2007

Lifestyle Modification Interventions

Modification Weight reduction Adopt DASH eating plan Dietary sodium reduction Physical activity Moderation of alcohol consumption SBP reduction (range) 520 mmHg/10 kg weight loss 814 mmHg 28 mmHg 49 mmHg 24 mmHg
Kaplan & Opie. Lancet 2006; 367:168-176

Goals of Therapy: JNC-7 & BHS-4

Reduce CVD (CHD, stroke, diabetes, CHF) and renal morbidity and mortality. Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease. Targets may be lower for subjects with low BMI , e.g., South Asians. Achieve SBP goal especially in persons >50 years age. Beyond BP control targets and strategies.
Gupta R. Black et al. Braunwalds Textbook of Hypertension 2008.

Beyond BP Control: Questions in Hypertension Management

1. Are there drug-specific benefits beyond BP lowering? 2. Are we trying to prevent end points or the disease process? 3. Most effective therapeutic strategy to reduce overall CVD risk burden. 4. Improving adherence to therapy.

Williams, B. J Am Coll Cardiol 2005;45:813-827

Which is Better: ACEIs, CCBs, BBs

Williams, B. J Am Coll Cardiol 2005;45:813-827

Which is Better: ACEIs vs CCBs

Why are ACE Inhibitors Better?

Benefits Beyond BP Control
Improvement in endothelial function Reduction in oxidative stress Decrease in vascular inflammation and adhesion molecules Inhibition of mitogenesis Regression of atherosclerotic plaques and LVH superior to older agents Inhibition of proteinuria superior to older agents Reduction in new onset diabetes Improvement in fibrinolysis

Evidence Based Molecules for Hypertension

ABCD Rule: British NICE Guidelines 2006
Younger <55 yr and non-Black Step 1 Step 2 Step 3 A A + C or D A+C+D Mono Two Multi drug Older >55 yr or Black C or D A + C or D A+C+D

Step 4 and Add: either betaMulti drug Add: either beta-blocker, Resistant HTN blocker, alpha-blocker alpha-blocker or or spironolactone or spironolactone or other other diuretic diuretic A= ACEI or ARB B= beta-blocker C= CCB D= Diuretic (THZ)
British NICE Guidelines. 2006

Issues in High BP Management

1. Are there drug-specific benefits beyond BP lowering? 2. Are we trying to prevent end points or the disease process? 3. Most effective therapeutic strategy to reduce overall CVD risk burden. 4. Improving adherence to therapy.

CV Risk Factor Clustering With Hypertension Framingham Offspring Study, Aged 18 to 74 Years
>50% of Hypertension Occurs in Presence of 2 or More Risk Factors
Men
1 RF 2 RFs 1 RF

Women
2 RFs

26% 19% 8%
No Additional RFs

25% 22%
3 RFs No Additional RFs

27% 17% 12%

24% 20%
3 RFs

4 or More RFs

4 or More RFs

Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S.

Risk of CHD in Mild Hypertension by Intensity of Associated Risk Factors

10-Year Probability of Event (%)
42 36 30 24 18 12 6 0 4 6 10 14 21 40

Risk Factors

SBP 150-160 mm Hg TC 240-262 mg/dL HDL-C 33-35 mg/dL Diabetes Cigarette smoking ECG-LVH

+ +

+ + +

+ + + +

+ + + + +

+ + + + + +

Kannel WB. Am J Hypertens. 2000;13:3S-10S.

The Polypill Concept

Majority of cardiovascular events occur in subjects with normal risk factor levels. To target prevention of intermediate and hard cardiovascular end-points in short- and long-term it is essential to shift the risk factor continuum to lower levels. Multiple risk factor interventions required to reduce acute events. Blood cholesterol and BP control is crucial. Original polypill: 3 anti-hypertensives (diuretics, enalapril, atenolol) Statin, aspirin and folic acid. Revised formulations Clinical concerns
Law & Wald. BMJ 2002; 324:1570-6 Wald & Law. BMJ 2003; 326:1419-22 Combination Pharmacotherapy Working Group. Ann Intern Med 2005; 143:593-99

Polypill Concept: Phase II Trial

TIPS. Lancet 2009; 373:1341-51.

Blood Pressure Lowering in TIPS

TIPS. Lancet 2009; 373:1341-51.

Beyond BP Control: Statins

Cholesterol Lowering Trialists Collaboration. Lancet 2005;366:1267-78

Benefits of Statins in Hypertension

Pleiotropic effects
Anti-inflammatory Anti-oxidant Anti-mitotic Anti-atherosclerotic

Vasculoprotective effects
Endothelial function Vasodilatory mechanisms Protective interleukins

Others

Lipid Lowering in TIPS

TIPS. Lancet 2009; 373:1341-51.

Beyond BP Control
Aspirin in Primary Prevention

Antithrombotic Trialists Collaboration. Lancet 2009;373:1849-60

Beyond BP Control: Folic Acid

Miller ER, et al. Am J Cardiol 2010;106:517-27

Polypill: Projected Benefits for CHD & Stroke

TIPS. Lancet 2009; 373:1341-51.

Issues in High BP Management

1. Are there drug-specific benefits beyond BP lowering? 2. Are we trying to prevent end points or the disease process? 3. Most effective therapeutic strategy to reduce overall CVD risk burden. 4. Improving adherence to therapy.

Prevalence, Awareness, Treatment and Control of Hypertension in Indian Women

Multicentric DST Study (4 urban, 5 rural sites; n=4608)
50 45 40 35 30 25 20 15 10 5 0
46.2

28.6

The Rule of Thirds (1/3)

56.8

Prevalence

Awareness Urban

Treatment

24.6

35.7 Control 46.5 28.3 10.2

Rural

Gupta R, Pandey RM, Misra A, et al. 2011

Hypertension Prevalence, Awareness, Treatment and Control Status in India

Parsi Community Study, Bombay (n=2879)
40 35 30 25 20 15 10 5 0 Prevalence Awareness Treatment Control

36.4% Treatment Gap, 36.4% Compliance Gap, 86.4% 63.6%

51.5%

13.6%

Bharucha & Kuruvilla. BMC Pub Health 2003; 3:e1

Determinants of Poor BP Control in India

Compliance with treatment** (Odds ratio 6.1, CI 3.9-12.6) Life stress (life event score, 4 vs. 1)** Smoking Alcohol intake High body mass index Others

** significant

Age, gender Educational status Occupation Marital status Socioeconomic status

Joshi PP, et al. J Hum Hypertens 1996; 10:299-303

Compliance with BP Medicines in UK Practice

Vrijens et al. BMJ 2008;336:1114-7

Contributing Factors for Noncompliance

Misunderstandings about the medication regimen Complexity of the medication regimen Adverse side effects Concerns about taking medications Patientphysician relationship Financial and social reasons
Thrall et al; J Human Hypertens 2004; 18:596-8

Strategies to Improve Compliance

Pharmacological therapy in hypertension Simplifying the medication regimen Appropriate drug selection dependent on patient characteristics Improved patientphysician communication Appropriate education Behavioral strategiesfor example, self-monitoring of BP, diary, memory cues, rewards Social supportfor example, family, health-care workers, physicians Continual monitoring of patient compliance by the physician
Thrall et al; J Human Hypertens 2004; 18:596-8

ABCDE Algorithm in Hypertension

Our modification
Younger <50 yr Step 1 Step 2 Step 3 Concomitant therapies A or B (if sympathetic hyperactivity) A (or B) + C or D or both A or B, C and/or D, add E Statins Mono Two Multi drug Older >50 yr A and/or C Add D A and C, and/or D, add B or E Statins

A= ACE inhibitors/angiotensin receptor blockers; B= beta blockers; C= calcium channel blockers; D= diuretics; E= extra drugs (central adrenergic agonists, direct vasodilators, alpha blockers, etc) Gupta & Guptha. Ind J Med Res 2011; In press.

Improving Management in Primary Care

Integrated approach to prevention and management. Public policies are important, eg, tobacco control, salt. Opportunistic case finding for risk factor assessment, early disease detection, and identification of high risk status Combination of pharmacological and psychosocial interventions, in a stepped care fashion needed. Long term follow-up with regular monitoring, and promoting adherence to treatment.
Beaglehole R, et al. Lancet 2008; 372:940-9

Conclusions
Hypertension is highly prevalent in India. There is low awareness, treatment and control status. Treatment is best achieved with combination of lifestyle measures and drugs. Two-drug combination is best option for BP control. Global CVD risk reduction is required to prevent events in all patients with hypertension. Addition of statins (and NOT aspirin or folic acid) to conventional BP therapy is useful for risk reduction. Compliance and adherence to treatment is a major issue.

No. in Millions
2.5 2 1.5 1.18 1 2.04

2.58

Million Death Study 1.90

1.59

25-30%

THANKS
0.5

GBD 1997 Projections

2010

1990

2000

2020