An Epidemiological Overview

• Cardiovascular disease (CVD) is the leading cause of death in the U.S.

• In 2005 CVD accounted for approximately 38 percent of all deaths

• CVD has been the number one killer in the U.S. since 1900 except for 1918 (influenza)

• More that 2,500 Americans die from CVD each day

• Among women, 1 in 2.6 deaths from CVD

Death Rates for Cardiovascular Disease, Including CHD and Stroke for Selected Countries

Heart DiseaseStrokeCancerChronic Lung Ds

Chronic NCDMorbidity/Mortality

Biologic Risk factors

SmokingUnhealthy DietPhys. Inactivity

Behavioral Risk Factors

GlobalizationUrbanizationPovertyLow EducationStress

Predisposing Environment

Blood Sugar

Blood Pressure

Cholesterol

BMI

Adopted Preventing Chronic Disease: A Vital Investment. WHO 2005

Increasing Prevalence of the Risk Factors for Non Communicable Diseases

Lancet 2011; 337: 680–89

Types Of Cardiovascular Disease

• Atherosclerosis

• Coronary heart disease (CHD)

• Irregular heartbeat (arrhythmia)

• Congestive heart failure (CHF)

• Congenital and rheumatic heart disease

• Stroke

Percentage Breakdown of Deaths from Cardiovascular Disease in the United States, 2001

Endothelial Dysfunction

From First Decade From Third Decade From Fourth Decade

Growth Mainly by Lipid AccumulationSmooth

Muscle and Collagen

Thrombosis Hematoma

FoamCells

FattyStreak

IntermediateLesion

AtheromaFibrousPlaque

Complicated Lesion/Rupture

Stroke

TIA

MI

Angina

High BP

Renal failure

PAD

Pepine CJ. Am J Cardiol. 1998;82:23S-27S.

Coronary Heart Disease

Arrhythmias

Congestive Heart Failure (CHF)

• Damaged or overworked heart muscle is unable to keep blood circulating normally

• Affects over 5 million Americans• Damage to heart muscle may result from:

rheumatic fever, pneumonia, heart attack, or other cardiovascular problem

• Lack of proper circulation may allow blood to accumulate in the vessels of the legs, ankles, or lungs

• Diuretics relieve fluid accumulation

Congenital And Rheumatic Heart Disease

• Congenital heart disease affects 1 out of 125 children born

• May be due to hereditary factors, maternal diseases, or chemical intake (alcohol) during fetal development

• Rheumatic heart disease results from rheumatic fever which affects connective tissue

Common Blood Vessel Disorders

Reducing Your Risk For Cardiovascular Diseases

• Risks you CAN control– Avoid tobacco– Maintain a healthy weight– Modify dietary habits– Exercise regularly– Control diabetes– Control blood pressure

• Systolic• Diastolic

– Control lipid• Cut back on saturated fat and cholesterol

– Manage stress

Reducing Your Risk For Cardiovascular Diseases

• Risks you CANNOT control

– Heredity

– Age

– Gender

– Race

Hypertension is the leading cause of death globally, especially in Asia

Ezzati and Riboli. N Engl J Med 2013;369:954-964Deaths attributable to individual risk factors

Physiology of Hypertension

• 3 key physiological mechanism lead to development of hypertension

1. Sodium/Volume

2. Renin Angiotensin Aldosterone System (RAAS)

3. Sympathetic Nervous System (SNS)

• Studies prove that drugs targeting Sodium/Volume (CCBs and DU) or the RAAS system fare better than SNS blockers in CV outcomes and BP control

• Even though SNS tone is higher in hypertensive than in normotensives, these results indicates that in most cases the SNSis not a driving force

The Journal of Clinical Hypertension 2012;14 (10 ); 657 - 64

Kaplan and Opie. Lancet 2006;367:168–76

Multiple Interactions among the Mechanisms of Controlling Blood Pressure

Pre-hypertensive Hypertensive +

Damage

Hypertensive +

Clinical Disease

Evolution of Hypertension

B. Williams. 2007

Number of Drugs

• Vasoconstriction

• Increased Peripheral Resistance

• Vascular remodelling

• RAAS and SNS Activation

Younger Older

• Declining GFR

• Sodium retention

• Increased Cardiac output

•Stiff Aorta – systolic hypertension

Plasma Renin

90.3% with 3 RFs

Most Hypertensive Patients Have Additional Risk Factors

a ≥140/90 mm Hg at baseline.RFs include: treated diabetes, diabetic nephropathy, ankle-brachial index of <0.9, asymptomatic carotid stenosis ≥70%, SBP >150 mm Hg, treated hypercholesterolemia, current smoking, men ≥65 y, women ≥70 y.REACH, Reduction of Atherothrombosis for Continued Health; RF, risk factor; SBP, systolic blood pressure.Bhatt DL et al. JAMA. 2006;295(2):180-189.

21

81.8%

Hypertensiona

N=67,888 patients aged 45 years or older from 44 countries

REACH Registry

Dzau et al. Circulation 2006;114:2850–70

Mancia et al. J Hypertens 2007;25:1105–87

Risk factors lead to increasing risk of organ damage

and clinical events: The cardio-renal continuum

• The risk associated with hypertension is greatly magnified by other CV risk factors, e.g.:– Hyperlipidemia

– Diabetes

– LVH

– Increased arterial stiffness

• The presence of such risk factors initiates pathological events and processes like oxidative stress and endothelial dysfunction which ultimately lead to overt organ damage and failure

• Many of these processes leading to CV and renal disease involve the renin-angiotensin system (RAS) and the actions of its most biologically active component – angiotensin II

From risk factors to organ failure:A continuous development

Dzau VJ, et al. Circulation. 2006;114:2850-70.

LV remodeling

MicroalbuminuriaChronic

Heart Failure

Stroke

MyocardialInfarction

TIA

Angina

LVH

IMT

End-StageRenal Disease

ModerateRenal Disease

Proteinuria

Mild RenalDisease

Clinical Disease

SubclinicalOrgan Damage

RiskFactors

CardiovascularEvent

End OrganFailure

Increased LDL

Diabetes/Metabolic Syndrome

Smoking

Hypertension

Diabetes

Diagnosis of Hypertension

• Office BP is recommended for screening and diagnosis of hypertension

• Diagnosis of hypertension should be based on at least two BP measurements per visit and on at least two visits

• Out-of-office BP should be considered to confirm the diagnosis of hypertension, identify the type of hypertension, detect hypotensive episodes, and maximize prediction of CV risk

• For out-of-office BP measurements, ABPM or HBPM may be considered, depending on indication, availability, ease, cost of use, and, if appropriate, patient preference

24

Mancia G et al. J Hypertens. 2013;31(7):1281-1357.

JNC V

Optimal110

120

130

140

150

160

170

180

190

200

210

220

JNC IV. Arch Intern Med. 1988;148:1023-1038.

JNC V. Arch Intern Med. 1993;153:154-183.

JNC VI. Arch Intern Med. 1997;157:2413-2446.

Chobanian AV et al. JAMA. 2003;289:2560-2572.

JNC I JNC II JNC III JNC IV JNC VI

Border-line

ISH

Stage 1 Stage 1

Stage 2

Stage 3

High-normal

High-normal

Normal Normal

Optimal

SBP

(mm Hg)

Normal

Border-line

ISH

Stage 4

No recommendations

for SBP in JNC I

or JNC II

JNC 7

Stage 1

Prehyper-tension

Normal

Stage 3

Stage 2

JNC I. JAMA. 1977;237:255-261.

JNC II. Arch Intern Med. 1980;140:1280-1285.

JNC III. Arch Intern Med. 1984;144:1045-1057.

Stage 2

Hypertension - JNC BP Classifications: SBP

JNC 8

80

85

90

95

100

105

110

115

120

125

130

JNC I JNC II JNC III JNC IV JNC V JNC VI

Considertherapy

Hyper-tensive

Mild Mild Mild

Stage 1 Stage 1

Moderate Moderate Moderate

Stage 2

Severe Severe SevereStage 3 Stage 3

Stage 2

Stage 4

High-normal

High-normal

High-normal

High-normal

Normal Normal Normal Normal

Optimal

DBP

(mm Hg)

Optimal

JNC 7

Stage 1

Stage 2

Prehyper-tension

Normal

JNC IV. Arch Intern Med. 1988;148:1023-1038.

JNC V. Arch Intern Med. 1993;153:154-183.

JNC VI. Arch Intern Med. 1997;157:2413-2446.

Chobanian AV et al. JAMA. 2003;289:2560-2572.

JNC I. JAMA. 1977;237:255-261.

JNC II. Arch Intern Med. 1980;140:1280-1285.

JNC III. Arch Intern Med. 1984;144:1045-1057.

Hypertension - JNC BP Classifications: DBP

JNC 8

Stratification of Total CV Risk Into Risk Categories According to BP, Risk Factors, and Comorbidities

2013 ESH/ESC Guidelines for the Management of Arterial Hypertension

28

BP, mmHg

Other Risk Factors,

Asymptomatic OD, or

Disease

High Normal

SBP 130-139

or DBP 85-89

Grade 1 HypertensionSBP 140-159or DBP 90-99

Grade 2 HypertensionSBP 160-179

or DBP 100-109

Grade 3 Hypertension

SBP ≥180or DBP ≥110

No other RF Low risk Moderate risk High risk

1 or 2 RFs Low risk Moderate riskModerate to

high riskHigh risk

≥3 RFsLow to

moderate riskModerate to

high riskHigh risk High risk

OD, CKD stage 3, or diabetes

Moderate to high risk

High risk High riskHigh to

very high risk

Symptomatic CVD, CKD stage ≥4, or diabetes with OD/RFs

Very high risk Very high risk Very high risk Very high risk

CKD, chronic kidney disease; CVD, cardiovascular disease; OD, organ damage.Mancia G et al. J Hypertens. 2013;31(7):1281-1357.

JNC 8 Guideline Treatment Recommendations and BP Goals

40

FDC, fixed-dose combination; aACEIs and ARBs should not be used in combination

James PA et al. JAMA. 2014;311(5):507-520.

Adult aged ≥18 years with hypertension

Implement lifestyle interventions (continue throughout management)

Set BP goal and initiate BP-lowering medication based on age,diabetes, and CKD

All agesDiabetes presentNo CKD

All agesCKD present with or without diabetes

BP goalSBP <150 mm HgDBP <90 mm Hg

BP goalSBP <140 mm HgDBP <90 mm Hg

Initiate thiazide-type diuretic or CCB alone or in combination

Initiate ACEI or ARB, alone or in combination with other drug class

Select a drug treatment titration strategy

A. Maximize first medication before adding second orB. Add second medication before reaching maximum dose of first medication or

C. Start with 2 medication classes separately or as FDC

Age ≥60 y Age <60 y

BP goalSBP <140 mm HgDBP <90 mm Hg

BP goalSBP <140 mm HgDBP <90 mm Hg

Initiate thiazide-type diuretic or ACEI or ARB or CCB alone or in combinationa

General population (no diabetes or CKD) Diabetes or CKD present

Nonblack Black All races

Different Classes of Drugs have Different Sites of Action

Beevers, et al. BMJ 2001;322:912–6;

McGhee, et al. Crit Care Nurse 2002;22:60–4;

Goodman & Gilman’s Pharmacological Basis of Therapeutics. 9th

ed. 1995.

ACEI = angiotensin-converting enzyme inhibitor;

ARB = angiotensin Type II receptor blocker;

CCB = calcium channel blocker

Different, but complementary mechanism of action

=

=

Totalperipheralresistance

β-blockers CCBsDiuretics ARBs ACEIs

X

Stroke

volumeHeart rate X

Cardiac

output

Venous

pressure

Arterial

pressure

BP

Increased 24-hour BPV has been associated with CV risk

Hansen TW, et al. Hypertension 2010;55:1049-1057.

Incidence of mortality and cardiovascular events by fifths of the distributions of the

systolic average real variability in 8,938 patients

BPV, blood pressure variability; CV, cardiovascular; NCV, non CV.

Guidelines on BPV

• NICE 20111

– Variability in SBP when measured visit-to-visit is a strong predictor of stroke, independent of mean SBP

– Whatever the underlying mechanisms, SBP variability appears to be an important independent predictor of clinical outcomes

• ESC/ESH guidelines 20132

– Consideration should be given to the evidence that visit-to-visit BPV may be a determinant of CV risk, independently of the mean BP levels achieved during long-term treatment, and that, thus, CV protection may be greater in patients with consistent BP control throughout visits

1. National Institute for Health and Clinical Excellence (NICE) Clinical Guideline 127. Available at: http://www.nice.org.uk/nicemedia/live/13561/56007/56007.pdf. 2. Mancia G, et al. Eur Heart J 2013;34:2159-2219.

BP, blood pressure; CV, cardiovascular; BPV, BP variability; SBP, systolic BP.

“Updated guidance recommends the best available evidence-based

treatment options to suppress BPV in people with hypertension”

Association between CV events and early morning period

1. Muller JE, et al. N Engl J Med 1985;313:1315–1322. 2. Marler JR, et al. Stroke 1989;20:473–476.

CV, cardiovascular risk; EMBPS, early morning blood pressure surge.

6:000:00 12:0018:00

Time of day

MBP surge as a cardiovascular risk

Kario K, et al. J Cardiovasc Pharmacol 2003;42 Suppl 1:S87-S91.

Morning surge

group (n=46)

Non-surge

group (n=145)

P-value

Age (years) 76 76 NS

24-h systolic BP (mmHg) 142 142 NS

Baseline data

Silent cerebral infarct

prevalence (%)

70 49 0.02

Number (/person) 2.0 1.5 0.01

Multiple cerebral infarcts

prevalence (%)

54 37 0.04

Prospective data

Stroke incidence (%)

(relative risk = 2.7)

17 7.0 0.04

A 10 mm Hg increase in morning surge in SBP

increased clinical stroke risk by 22%

MBP, morning blood pressure; SBP, systolic blood pressure.

BPV and MBP surge are very

important and should be targeted

Therefore the class of antihypertensive which can control

BPV and MBP surge should be the initial treatment of choice

Which class of antihyperintensives?

CCB, ARB, ACEI, diuretics

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BPV, BP variability; CCB, calcium channel blocker.

New Weapons Against Heart Disease

• Techniques for diagnosing heart disease– Electrocardiogram (ECG)– Angiography– Single positron emission color tomography

(SPECT)– Radionuclide imaging– Magnetic resonance imaging (MRI)– Ultrafast CT– Digital cardiac angiography (DSA)

Angioplasty Versus Bypass Surgery

• Angioplasty – a thin catheter is threaded through the blocked arteries. The catheter has a balloon on the tip which is inflated to flatten the fatty deposits against the wall of the artery

• Coronary bypass surgery – a blood vessel is taken from another site and implanted to bypass blocked arteries and transport blood

Aspirin For Heart Disease?

• Research shows that 80 milligrams of aspirin every other day is beneficial to heart patients due to its blood thinning properties

• Some side effects of aspirin: gastrointestinal intolerance and a tendency for difficulty with blood clotting

• Should only be taken under the advice of your physician

Thrombolysis

• If victim reaches an emergency room and is diagnosed quickly, thrombolysis can be performed

• Thrombolysis involves injecting an agent such as tissue plasminogen activator (TPA) to dissolve the clot and restore some blood flow

Summary

• CV diseases are the leading cause of deaths globally

• There are numbers of risk factors that can be controlled to prevent CV diseases

• Hypertension is one of the important risk factor which could be managed

• Blood Pressure Variability and Morning BP Surge are associated with CV risk