High Blood pressure has multiple adverse reaction on different body system and its proper management causes beneficial effect in multiple co morbid condition.

1. Blood pressure management in
cardiovascular protection
DR NASIR UDDIN
MD (Cardiolgy)
Department of Cardiology
Dhaka Medical College

2. CV diseases
continuum
Hypertension
- One of the key
beginners of all
damages
J Cardiol Curr Res 2016, 5(1): 0015

3. Hypertension: a global burden in the world
1. Mills KT, Stefanescu A, He J. Nat Rev Nephrol. 2020;16:223-237.
2. World Health Organization. Hypertension. September 2019. Available at: https://www.who.int/news-room/fact-sheets/detail/hypertension. Accessed 14 April 2020.
1.13
billion
HYPERTENSIVE PATIENTS
most (two-thirds) living in low- and
middle-income countries²
The prevalence of hypertension
has increased over the past four
decades, especially in low- and
middle-income countries1

4. Hypertension is the leading cause of death
worldwide1
1. Ezzati M et al. N Engl J Med. 2013;369:954-964. 2. Unger T et al. J Hypertens. 2020;38:982-1004.
Deaths
10.4 million
deaths
each year²
High blood pressure
Smoking and secondhand smoke
Diets low in fruits
High BMI
High blood glucose
Physical inactivity and low physical activity
High dietary salt
Alcohol use
Diets low in nuts and seeds
High serum cholesterol
Diets low in vegetables
Diets low in whole grains
Diets low in fish and seafood
0 2 000 000 4 000,000 6 000 000 8 000 000 10 000 000
Deaths attributable to individual risk factors

5. Hypertension leads to CV disease and premature death
CV: cardiovascular; IHD: ischemic heart disease; SBP: systolic blood pressure.
Mills KT, Stefanescu A, He J. Nat Rev Nephrol. 2020;16:223-237.
Causes of deaths worldwide attributed to hypertension in 2015
0
2000
4000
6000
8000
IHD Ischemic
stroke
Hemorrhagic
stroke
Other
cardiovascular
diseases
Chronic kidney
disease
Deaths
(thousands)
3573
1134
1423
1151
553

6. Hypertension is a silent killer1
1. World Health Organisation. A global brief on hypertension Silent killer, public health crisis. Available at:
https://www.who.int/cardiovascular_diseases/publications/global_brief_hypertension/en/. Published April 2013. Accessed April 16, 2020. 2. Chow CK et al. PURE Investigators. JAMA.
2013;310(9):959-968.
1 out of 2 people
with hypertension doesn’t
know they have it²

7. Prevalence
 The prevalence of hypertension is higher in low- and
middle-income countries (31.5%) than in high-income
countries (28.5%). Bangladesh is one of those low- and
middle-income countries.
 Hypertension has been attributed to be responsible for
13% of global deaths. With the projection of a 30%
increase in worldwide prevalence of this condition by
the year 2025
1 2
3
Ref: Clinical Hypertension (2020) 26:10

8. Key facts for Hypertension & CVD

9. Relationship of blood pressure to cardiovascular diseases
• The relationships between blood pressure and cardiovascular morbid and mortality have
been addressed in a large number of observational studies.
• Office blood pressure shows an independent continuous relationship with the incidence
of several cardiovascular events such as stroke, myocardial infarction, sudden death,
heart failure, and peripheral arterial disease as well as of end stage renal disease.
• This has been shown for all ages and in all ethnic groups
Ref: Pharmacological Research (2018)

10. Relationship of blood pressure to cardiovascular
• Systolic blood pressure is a stronger predictor of events than diastolic BP after the age of
50 years and in the elderly pulse pressure has an additional prognostic role.
• Isolated systolic hypertension has particularly high cardiovascular risk.
• A continuous relationship with cardiovascular events is also exhibited by out-of-office
blood pressures obtained by 24-hour ambulatory blood pressure monitoring and home
blood pressure measurements.
Ref: Pharmacological Research (2018)

11. Hypertension and total cardiovascular risk
• Chronic hypertensive state causes cardiac hypertrophy which is an independent risk factor for
myocardial infarction.
• Left ventricular hypertrophy is associated with increased oxygen demand leading to the
development of new arterial vessels (collaterals) to supply the myocardium.
• This collateral circulation, driven by pressure gradient, is more effective in the subepicardial
layer than in subendocardial layer, which therefore results in being more exposed to ischemia
and infarction.
• During an acute coronary ischemic event, reduce systolic blood pressure and decreased wall
tension of ischemic area results in patency of small vessels, giving some blood supply to the
ischemic area.
• On the other side, large reduction of diastolic blood pressure more often leads to ischemia,
despite the lack of total vessel occlusion
Ref: Int J Hypertens. (2011)

12. Hypertension and Myocardial Infarction
The relation between HTN and myocardial infarction can be mainly explained underscoring
two key factors:
1. Common risk factors shared by the two diseases, such as genetic risk profiles, insulin
resistance, sympathetic hyperactivity, and vasoactive substances (i.e., angiotensin II)
2. Hypertension is associated with accelerated atherosclerosis, which contributes to
progression of myocardial infarction
Ref: Int J Hypertens. (2011)

13. Pathophysiological factors that
link hypertension and acute
myocardial infarction
Ref: Int J Hypertens. (2011)

14. Hypertension and Heart Failure
• Chronic HTN causes structural and functional changes in the heart that ultimately lead
to HF, which further increases mortality and morbidity.
• Although treating high BP intensively prevents and reverses myocardial changes in
patients at risk of HF, defining the optimal BP target for patients with established HF is
challenging, because the evidence is inconsistent and scarce.
Ref: Oh and Cho Clinical Hypertension (2020)

15. Pathophysiology of hypertensive heart disease
• High BP increases the left ventricular (LV) afterload and peripheral vascular resistance,
and prolonged exposure to an increased load leads to pressure- and volume mediated
LV structural remodeling.
• Ventricular hypertrophy is an initial compensatory mechanism in response to the chronic
pressure overload that preserves the cardiac output and delays cardiac failure.
• The remodeled left ventricle is likely to decompensate, and HF can develop as a
consequence of increased LV stiffness and the presence of diastolic dysfunction.
Ref: Oh and Cho Clinical Hypertension (2020)

16. Pathophysiology of hypertensive heart disease
Ref: Pathobiology of Human Disease: A Dynamic Encyclopedia of Disease Mechanisms

17. Treatment of hypertension in patients with heart failure
• Treating high BP is more complicated in patients with established HF, but it remains important
with respect to HF progression and patients’ prognoses.
• As all medications that have favorable effects on HF outcomes lower BP to some extent, we can
assume that a close relationship exists between BP and HF outcomes.
• The PARADIGM (Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with
an angiotensin-converting enzyme (ACE) inhibitor to Determine Impact on Global Mortality and
Morbidity in Heart Failure) study findings show that, although the benefit of sacubitril/valsartan
over enalapril was still evident in patients with SBP < 120 mmHg, it was significantly more
decreased than those with SBP ≥120 mmHg.
Ref: Oh and Cho Clinical Hypertension (2020)

18. Role of hypertension on stroke
• Hypertension is the most prevalent risk factor for stroke, based on data from 30 studies, and has
been reported in about 64% of patients with stroke.
• Patients with hypertension exhibit higher risk for ischemic stroke and hemorrhagic stroke
compared with patients without hypertension, particularly in those with poor blood pressure
control.
• The risk of stroke appears to follow a linear curve with 6–7% increase risk per 10 mmHg increase
in systolic blood pressure.
Ref: Acta Cardiologica (2021)

19. Impact of hypertension control on stroke
Ref: Acta Cardiologica (2021)

20. Blood Pressure Levels in Patients with Stroke Suggested by the Current
Clinical Guidelines
Ref: European Cardiology Review (2019)

21. HTN and AF
• Patients with hypertension have 1.7-fold higher risk of
developing AF than normotensive individuals, and 1 in 6 cases
of AF has been attributed to hypertension.
Mihail S et al. Hypertension. 2017;70:854–861

22. HTN and SCD
• In hypertensives, sudden cardiac death constitutes 27-60% of all
cardiovascular deaths.
• In a cohort of 3242 patients with average follow up of 10.3 yrears
shows that compared with the survivors, those who die suddenly
have higher blood pressure.
• During follow-up, SCD occurred in 33 patients at a rate of 0.10 per
100 patient-years (95% CI, 0.07-0.14).
• The rate of SCD was 0.07 and 0.30 per 100 patient-years,
respectively, in the cohort of patients without and with ECG left
ventricular hypertrophy ( P<0.01).
von Brandis P,. 1997 Jun 20;117(16):2337-40. Norwegian. PMID: 9265281.
Verdecchia P, Hypertension. 2019 May;73(5):1071-1078.

23. HTN and CKD
• A Prospective Study of 23,534 Men and Women in Washington
shows that the adjusted hazard ratio (95% confidence interval)
of developing CKD among women was
• 2.5 (0.05 to 12.0) for normal BP
• 3.0 (0.6 to 14.4) for high-normal BP,
• 3.8 (0.8 to 17.2) for stage 1 hypertension
• 6.3 (1.3 to 29.0) for stage 2 hypertension,
• and 8.8 (1.8 to 43.0) for stages 3 or 4 hypertension compared
with individuals with optimal BP.
Melanie K. Haroune et al. JASN November 2003, 14 (11) 2934-2941;

24. HTN and PAD
• Hypertension is a risk factor for vascular disorders, including
PAD.
• Of hypertensives at presentation, about 2-5% have intermittent
claudication, with increasing prevalence with age.
• 35-55% of patients with PAD at presentation also show
hypertension.
Clement DL et al. Curr Pharm Des. 2004;10(29):3615-20.

25. Hazard ratio of hypertension & myocardial infarction
Ref: Journal of the American Heart Association (2021)

26. Hazard ratio of hypertension & heart failure
Ref: Journal of the American Heart Association (2021)

27. Hazard ratio of hypertension & stroke
Ref: Journal of the American Heart Association (2021)

28. Hazard ratio of hypertension & all death
Ref: Journal of the American Heart Association (2021)

29. An interesting fact: White coat hypertension (WCH) is associated
with an increased risk for cardiovascular events
Persons with untreated WCH, but not those with treated WCE, have a markedly increased risk for
cardiovascular events and all-cause mortality compared with persons with normal BPs.
Ref: Ann Intern Med. (2019)

30. 2 in 3 treated hypertensive patients have
uncontrolled BP
BP: blood pressure.
Chow CK et al. JAMA. 2013;310:959-968.
In EU, Coveram® is indicated as substitution therapy in patients already controlled with perindopril and amlodipine. To be approved by local RA.
BP control rate in the PURE study (%)
0
5
10
15
20
25
30
35
40
45
40.7
32.3
26.9
40.2
32.5
High-income
country
Upper-middle-
income country
Low-middle-
income country
Low-income
country
Overall
International, multicenter,
cross-sectional study
of adults with hypertension
(n=153 996).

31. Treating and not controlling hypertension
lead to dramatic consequences
Zhou D et al. Scientific Report. 2018;8:9418.
In EU, Coveram®® is indicated as substitution therapy in patients already controlled with perindopril and amlodipine. To be approved by local RA.
Study that investigated
the association of controlled
and uncontrolled hypertension,
and the role of treatment,
with the risk of all-cause
and CVD mortality using
a prospective cohort
of a nationally representative
sample of US adults.
Cerebrovascular disease
CVD Heart disease
Hypertension status
No hypertension
Treated and controlled
Treated but uncontrolled
Untreated
0 50 100 150 200 250 300
.975
.980
.985
.990
.995
1.000
Probability
of
survival
(%)
0 50 100 150 200 250 300
.980
.985
.990
.995
1.000
Time to event (months)
0 50 100 150 200 250 300
.996
.998
1.000

32. 24-hour BP is a better CV risk predictor than office BP
CV: cardiovascular; SBP: systolic blood pressure.
1. Mancia G, Verdecchia P. Circ Res. 2015;116:1034-1045. 2. Staessen J, et al. JAMA. 1999;282:539-546; 3. Dolan E et al. Hypertension. 2005;46:156-161.
4. Sega R et al. Circulation. 2005;111:1777-1783.
Relationship between office BP or 24-hour average SBP
with CV events or mortality in 3 studies: SYST-EUR study, Dublin study,
and PAMELA population study1
Review paper highlighted
relationship between office BP or
24-hour average SBP with CV
events/mortality in three studies1
Systolic Hypertension in Europe
study (SYST-EUR) in patients
with uncontrolled isolated
systolic hypertension, n=808,
≥60 years old.2
Dublin study: n=5 292,
untreated hypertensive patients3.
Pressioni arteriose monitorate
e loro associazioni (PAMELA)
population study:
n=2 051, general population4
Office
24-hour
80 120 140 200 220
0
0.1
0.2
2-yrs
risk
of
CV
events
100 180
160
SYST-EUR
90 130 150 210 230
0
3.0
3.5
5-yrs
risk
of
CV
death
SBP (mm Hg)
110 190
170
2.5
2.0
1.5
1.0
0.5
DUBLIN
80 120 140 200 220
0
30
60
100 180
160
50
40
20
10
240
11-yrs
risk
of
CV
death
PAMELA

33. Less BP variability leads to a better clinical
outcome
BP: blood pressure.
Diagram adapted from Mancia G et al. Hypertension. 2007;50:299-305.
Posthoc International Verapamil
SR-Trandolapril Study analysis,
in which we determined whether adverse
outcomes are related to consistency of BP
control. A total of 22 576 patients with
hypertension and coronary artery disease
were divided into 4 groups according
to the proportion of visits in which BP
was in control.
BP variability
Visits with BP control
(<140/90 mm Hg)
<25%
High
0
Death,
nonfatal
myocardial
infarction,
or
nonfatal
stroke
(%)
20
15
25 to <50%
Moderate High
50 to <75%
Moderate Low
≥75%
Low
5
10
(n=3 839) (n=3 757) (n=6 664) (n=8 316)
15.0
10.8
9.2
8.1

34. "Cardiovascular protection by antihypertensive treatment could be potentiated
if therapy is targeted not only at achieving control of the average blood
pressure values, but also at stabilizing blood pressure variability
in the long term, by reducing blood pressure fluctuations between clinic visits."
Increasing blood pressure variability is a strong
predictor
of cardiovascular morbidity
Parati G et al. Hypertension. 2013;62:682-684.

35. Central SBP predicts cardiovascular mortality
better than brachial BP
BP: blood pressure; CV: cardiovascular; HRs: Harzards ratios; PP: pulse pressure; B-PP: brachial pulse pressure; C-PP: central pulse pressure;
B-SBP: brachial systolic blood pressure; C-SBP: central systolic blood pressure.
Wang KL et al. J Hypertens. 2009;27:461-467.
Only central SBP and brachial pulse
pressure independently
contributed to CV mortality
Study cohort of 1 272 normotensive
and untreated hypertensive participants
from a previous community-based survey
used to assess cardiovascular mortality
Cardiovascular mortality
0.5
B-SBP
C-SBP
C-PP
B-PP
2.0
1.0 1.5
HRs

36. protection against CV events and death
CV: cardiovascular; MI: myocardial infarction; CAD: coronary artery disease; EP:end point.
1. Dahlöf B, et al. Lancet. 2005;366:895-906. 2. Bertrand ME, et al. Am Heart J. 2010;159:795-802. 3. Pepine CJ, et al. JAMA. 2003;290:280516.
4. Jamerson K, et al. N Engl J Med. 2008;359:2417-28. 5. Mancia G et al. Eur Heart J. 2013;34:2159-2219.
Combination regimen Trials Study design Results
Perindopril/amlodipine
vs atenolol/thiazide
ASCOT1
19 257 patients with hypertension + 3 cardiovascular risk
factors included in an international, multicenter,
prospective randomized open-blinded trial
for an average of 5.5 years
 CV mortality: - 24% (P=0.001)
 Total mortality: - 11% (P=0.02)
 Primary EP: -10% in non fatal MI and coronary mortality (P=0.1052)
Perindopril/CCB
vs CCB alone
(post-hoc analysis)
EUROPA
CCB2
Multicenter, double-blind, placebo-controlled,
randomized trial recruiting patients with stable CAD. 1
022 patients received perindopril/CCB and 1 100 patients
placebo/CBB during 4.2 year follow-up.
 CV mortality: nonsignificant
 Total mortality: - 46% (P<0.01)
 Primary EP: -35% on composite of CV mortality, nonfatal MI,
and resuscitated cardiac arrest by 35% (P<0.05 vs placebo)
Verapamil/trandolapril
vs atenolol/HCTZ
INVEST3
Randomized, open label, blinded end point study
of 22 576 hypertensive CAD patients which was
conducted over 5.5 years in 14 countries.
 CV mortality: nonsignificant
 Total mortality: nonsignificant
 Primary EP: nonsignificant (first occurrence of death, nonfatal MI, or nonfatal stroke)
Benazepril/amlodipine
vs benazepril/HCTZ
ACCOMPLISH4
Randomized, double-blind trial, including 11 506 patients
with high-risk hypertension receiving either
benazepril/amlodipine or benazepril/HCTZ
 CV mortality: nonsignificant
 Total mortality: nonsignificant
 Primary EP: -20% (P<0.001) Composite of death from CV causes,
nonfatal MI, nonfatal stroke, hospitalization for angina, resuscitation after
sudden cardiac arrest, and coronary revascularization.
Valsartan/amlodipine No trial5 ---
"… (the combination of) an angiotensin receptor blocker
and a calcium antagonist is never systematically used
in an outcome trial…"5
Olmersartan/amlodipine No trial5 ---
Telmisartan/amlodipine No trial5 ---

37. ACEis have a consistently significant and higher benefit in terms
of all-cause mortality reduction in different patient groups vs
ARBs
ACEi: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker; CAD: coronary artery disease; MI: myocardial infarction; RAAS: renin–angiotensin–aldosterone system.
1. van Vark LC et al. Eur Heart J. 2012;33:2088-2097. 2. Lv J et al. Cochrane Database Syst Rev. 2012;12:CD004136. 3. Baker WL et al. Ann Intern Med. 2009;151:861-871.
4. Savarese G et al. J Am Coll Cardiol. 2013;61:131-142. 5. Hara M et a. OACIS Investigators. Am J Cardiol. 2014;114:1-8.
Meta-analyses assessed
the impact of ACEIs and ARBs
on mortality in different patient
groups
Hypertension
ACE inhibitors
ARBs
Diabetes
ACE inhibitors
ARBs
CAD
ACE inhibitors
ARBs
High-risk
ACE inhibitors
ARBs
Post-MI
ACE inhibitors
ARBs
Van Vark et al. Eur Heart J. 2012.1
158 998 patients
Lv et al. Cochrane Database. 2012.2
61 264 patients
Baker et al. Ann Intern Med. 2009.3
37 148 patients
Savarese et al. JACC. 2013.4
108 212 patients
Hara et al. Am J Cardiol. 2014.5
9 025 patients
0.9 1.0 1.2
1.1 1.3
0.8
0.7
Favors RAAS blocker Favors comparator
MORTALITY REDUCTION

38. Summary
• Hypertension is the strongest risk factor for almost all different cardiovascular
diseases.
• The prevalence of hypertension as well as cardiovascular risks are increasing day by
day.
• Blood pressure control is one of the important factor to reduced cardiovascular
morbidity & mortality.
• Consistent blood pressure controlling is the key factor for any kind of cardiovascular
health.